Fallout: Tactics is set in the Midwest. A BoS expedition is sent to explore the Midwest. Things go to shit and they end up stuck there with limited resources, so they start recruiting the local riff-raff in to the BoS. One thing leads to another and they end up fighting an escalating series of increasing weird factions. It turns out all the chaos is being driven by a serious threat that could overrun the whole midwasteland. The BoS troops recruit a ragtag armor of super mutants, deathclaws, ghouls, tribals, psychics, and robots to fight their way to the core of the problem and save the wasteland.
It's a fun game, very solid squad based tactics using the SPECIAL system, inventive enemies, lots of fallout weirdness.
I’d really like to see a competent game developer tackle the Midwest BoS because by the end of the game (and the most likely canon ending of the BoS destroying the calculator) they’ve changed so much, running out of tech, recruited various unusual recruits as mentioned and accidentally governing chunks of area. An entirety different group to the old and new BoS of other games.
Some friends and I worked this out and what we came up with was that the everglades would take over most of florida, and the player would use a customizable airboat to travel around.
Caesar's Legion was from the Midwest, they fled there after the NCR defeated them in a surprise attack, during a saturnalia style orgy during the First Battle of Hoover Dam. There were also radio-active twisters present all across the midwest, which prevents makes travel for certain seasons improbable. This was all before the Bethesda times, however.
Chicago has an enclave outpost likely, there is a brotherhood chapter in montana and outside of chicago. More besides the game-that-shall-not-be-named we do not know about the midwest.