I'm not sure if this is the place for this but I'm currently working on a homebrew campaign set in the Fallout universe. As all of my players, and myself are from the DMV area I was planning on setting it in Baltimore and the surrounding areas. Obviously. Setting-wise, it wouldn't be too different from FO3 and the capital wasteland but story-wise, I'm stuck. I can't think of a good overarching plot for the campaign. Any help would be greatly appreciated. 

The thing I always loved about Fallout was its compatibility with fantasy-style storytelling. You could adapt most fantasy plots into Fallout with little difficulty. The magical McGuffin the evil wizard tries to use to rule the world becomes a potent, forgotten piece of pre-war tech. The all powerful diety could be some brain-in-a-jar connected to heaps of machines they used to survive the war. The paladin could be a literal paladin with the brotherhood of steel, sworn to protect ancient knowledge from ever being abused again. 

One of the reasons for this is that a lot of fantasy stories have inherently post-apocalyptic themes baked in anyways: living in a time after a great calamity, living in the ruins of a more-advanced ancient civilization, wide stretches of the world unsettled and populated by dangers, outcasts, and monsters, it's all there. 

When you start to think of it in terms of that compatibility between genres, it may be easier to come up with a story you want to tell. 

An alchemist has found a new substance, that can control the plants and animals of the world. Many people use this for good, but some have used it to bend creatures to their will, and perform acts of evil. 

I'm having a hard time combining the Fallout Universe with the D&D5E rule set (there are more easily adjusted rules sets to use) but it's an interesting idea so I'll give it a shot.

For low-level characters or conflicts you have the standard (both i Fallout and D&D) quests of go there, fetch that, give it to those people over there. This was pretty much the whole of FO3 and 4 so you can't really go wrong with that. ;)

If you want something bigger and more epic I suggest having some infighting in one or more of the established factions in your area. Maybe the local government is having an election and both sides, even though well-meaning, use whatever means they can to win? Or the local BoS chapter just had its leader murdered but the killer had good reasons which splits the chapter in two? 
Meanwhile while all of this is going on, there are also rumours of a new disease spreading between settlements. Some dismiss it as just radiation sickness ("a sip of radaway will cure that!") but others are not so sure. AT the same time deathclaws and feral mutants have started migrating towards the area for some unknown reason. And what's up with that time capsule that was found buried outside the old University? Can that have anything to do with something? 

Those are actually good jumping off points, thanks! Out of curiosity what other systems would you say work better with the FO universe?

GURPS, given that the original Fallout game was intended to be GURPS.  Really, any system that uses a point-buy character creation instead of character classes would probably work better.

Any system that focuses on guns and mutations over fantastical races and magic, really. GURPS has already been mentioned. Depending on how much re-flavourng you want to do, the 40K/Rogue Trader game could also work. Google "post-apocalyptic RPG" and look around for one that you think suits your needs.

someone else made "D&Z", a zombie adaption of 5e. I don't play fallout, but I think it's closer to what you are going for.

search the forums for it

I'm from DE (mostly upper but a couple years here in middle) so the idea of something set in the DMV area is just awesome. And I'm a HUGE Fallout fan. So like. Hell yeah. Feel free to DM me to talk more ideas if you want, but here are some initial thoughts:

Maybe feature the DuPont family and whatever AstraZenica would turn into. The News Journal. 99.5 WSTW as a major news station. WJBR for classical music in the region. Obviously these are more modern things but you could totally claim they would have came around in the Fallout Verse.

Perhaps AstraZenica still developed around pharmaceutical research, but over time it became a FEV research center that, over time, developed its own unique strain of FEV and Super Mutants post-apocalypse. Perhaps they developed a way to turn people into ghouls with a higher chance of not becoming feral; mayhaps the DuPont family even went in on it and are now all ghouls living in their estate in Beaver Valley and are secretly controlling the region.

Some of the best advice I know of about building a campaign plot comes down to this piece of advice, from HowToBeAGreatGM (Youtube & his own website): "Someone wants something badly by a certain time and is having trouble getting it." Then you structure the story into 4 arcs: Getting Stuff, Building Stuff, Testing Stuff, Achieving Goal.

So, start by building that sentence. Give your Big Bad a name (maybe an enemy of the DuPonts; can always change it later), and a goal (can be an abstract concept, such as "wants the nuclear core" - don't even need the reason yet but you will need to decide that before too long), and a deadline ("before the reactor's cooling system fails, which it is on course to do" or whatever), and why they're having trouble getting it ("it's absolutely infested with thousands of feral ghouls, super mutants, rad creatures, etc" or "is locked away in a vault that is nigh invulnerable" or "is in a cache of technology that the Brotherhood are currently going after" or whatever). As far as the reason goes, it could be personal ("want to fuel a personal generator in a private vault for the rest of time"), altruistic ("want to fuel a massive water purifier"), greedy ("want it to power the massive slave complex they own") or anything like that.

You can build the rest around what your party does, but I like having the party start off as working unknowingly for the bad guy, at least at first - and hopefully for as long as you can get away with hiding their true intentions. Make sure you create minion NPCs of varying levels that work for the BBEG that are doing their dirty work for them, and create subplots from there. Using the above example, perhaps your plot involves finding the special AstraZenica strain of Ghoulification that the DuPont family have kept hidden for themselves - in order to create intelligent ghoul minions who can go into the site that is swarmed with ghouls and radiation. A minion NPC hires the party to do this, though this minion might not be being completely honest with the party. You could structure that part of the plot easily with something like this:

• Minion "Saul" is ordered by the BBEG to find this strain. He is given information that the DuPont family may have a delivery caravan delivering this strain to them from the AstraZenica complex. The minion decides to hire a group in order to collect that strain, but in order to avoid greedy n'er-do-wells that might steal it for themselves, he hires a group less likely to do that, and tells them that it's a dangerous delivery of FEV to a criminal group that he won't give too many details about.
• The PC group find this delivery caravan, take them over, and maybe find notes about who the sample is actually going to - the DuPont family. They can then choose to take it back to their employer, or take it to the intended recipient, leading into two very different directions. They might even go to AstraZenica to find out what this really does, or experiment with it themselves!
• If they go to the DuPonts, the DuPonts become their new employers, asking the party to rat out their previous employer and find out why he wanted this for himself. If they take it back to Saul, Saul will then tell them to return to him in a few days/couple weeks/whatever (side-quest time); during which time Saul will get orders from the BBEG to find test subjects to test the serum out on to ensure it works, which is the PCs' next job. (When having the PCs unknowingly working for the bad guys, their quests get progressively more evil until the party realizes what they're doing.) The PCs then told to take a portion of the sample to a scientist in some nearby-ish colony and to give them sealed instructions. (If the party opens the instructions, it tells the scientist to create a gas dispenser of this sample.) If they go through with that, they are then contacted and told to take this "special device" to a nearby camp of "wastrels and lepers" and to plant it and leave immediately.
• Obviously, what happens next if they don't go a different path, is the gas is released and the camp is turned into feral ghouls that, if the party are nearby, immediately become a threat. Upon reporting back to Saul, they'll be told that was not the intended effect - and that the sample must be bad. He might even lie about the intended use of the sample, or he might be honest and say it's to turn "the sick and unsavable" into "intelligent ghouls".
• If the party continue to work with him after all this, they will be then instructed (and paid very well) to infiltrate the AstraZenica lab and secure another, better sample of this. They are then directly put against AstraZenica and it's DuPont-payrolled guard, whom they could potentially talk with and change sides to. If not, they steal the sample, and take it back to the same scientist - or a different one further away in dangerous territory - who synthesizes it properly. Naturally, the next stage is to test it again - and this time it works. The next step is to use it on a larger population, and then for Saul to find a way to convince that population to work for his employer - possibly "for a cure" (that doesn't exist; perhaps the PCs are also told during all this time that Saul's employer is secretly looking for a way to reverse the effects of ghoulification, and are put on some pointless side-quests at this time that involve taking more samples to different groups; if any of the major FO factions hear of this, like the Brotherhood, they would definitely interfere).
• Obviously, not everyone would agree to work for him, but with enough people willing to Saul now has himself a group who can make the attempt to get into the radiation-heavy ghoul-infested area and make the first attempt to retrieve the reactor core - which will fail. They need people who are capable of taking down these ghouls, possibly with help. So the next goal is to ghoulify the party themselves, as they've proven capable. In order to do this, Saul might trick the party, or capture them, or pay them, or try to convince them it's important. He might lie and say they've got a cure being synthesized by one of the sidequest-scientists mentioned earlier and guarantee that it's reversible - with a huge paycheck to boot. Maybe he blackmails them with their pasts in some way. Either way, that's the attempt - and it may or may not succeed.
• If Saul fails, he finds another strong group to do this to, a few of which are put out to eliminate the PCs to tie up that loose end; meanwhile, another group of the same stronger group are sent to recover the reactor core. By this point, there should have been some logs or terminals the PCs have gotten into that hint at the ultimate goal of Saul/Saul's boss. So the PCs now have to contend with a merc group hunting them down (Talon Company survivors anyone?) as well as figuring out how to stop Saul.
• The ENTIRE TIME this is going on, the BBEG has had ANOTHER minion (or two, or three) doing similar things - possibly with FEV, or heavy radiation, or even the same ghoulification samples. This is why Saul is a minion and not the BBEG. The BBEG is paying the most in prestige, slaves, power, caps, technology, etc to whoever gets the job done first, but they are soooorta told to "work together" so it's a "friendly" rivalry competition thing. That ensures that if Saul is taken out early, other minions of the BBEG are still going around doing the same thing - and you aren't out your entire plotline. This also ensures that there are things going on in the background of the plot to make your world feel alive and as if things are happening even if they don't directly cross the PCs' paths. The PCs could even encounter some of these other groups.
• Ultimately, it's possible that no groups are capable of getting what the BBEG wants and he decides to do something drastic - like make his strongest minions, such as Saul or the others, into super mutants with a unique strain of FEV or special ghouls with the serum, or even HIMSELF. He might make hundreds of slaves do it. The possibilities are endless, but in the end, it's possible he does it himself - and doing so creates a BBEG that the party can fight against, literally.
• During all of this, various side-quests could easily and organically pop up. Perhaps some of these scientists are in radiation-heavy areas, such as one being with the Children of Atom. They need to get radiation suits or Power Armor, which is a side-quest of its own - you can't just buy them, obviously, you have to find them in a raider-run warehouse, or in a warehouse that's right near a deathclaw nest, or secure a working relationship with the Brotherhood, or any other number of things.

Obviously, a lot of "ifs" up there, but that's how it goes. The party could change their minds at any point, and are likely to depending on the information. They could decide to run right off out of the region and try to take up a venture to the Mojave. They could decide that they don't want to work for any of the factions you've developed for the plot. They might decide to experiment with things themselves and see what happens. So ultimately, just make sure that things are going on in the background that you can push the PCs towards no matter what they're doing - or at least have them there for the PCs to encounter.

Since you're basing the setting on Fallout 3, you could use the Fallout 3 storyline.

Someone actually made a Fallout 5e conversion.  Don't think I'm allowed to link it on the forums, but a quick search generally finds the page.

Yeah it’s by XP to Level 3. It’s actually really well made!