My Idea
OK so in Fallout New Vegas there is a location called the Mojave outpost if you go in the back there's a locked gate if you look it up it's sorta like a border between The Mojave Wasteland and The Core Region so what if Bethesda makes a Dlc that allows you to venture into the core region to explore and mainly do side quest's.
Story: I thought of a storyline In fallout 3 The Enclave are no longer considered a threat to the West Coast but that doesn't mean that there no longer active in America. Your contacted by a former Enclave scientist that left the Enclave because he thought what they were doing is immoral. He tells you that there base of operations are in the Core Region they are going to release a next generation of super mutants faster, stronger, smarter and have the ability to spread it over the entire region its the couriers job to stop it.