The Midwest refers to the former north-central states of the United States of America, specifically Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Ohio, Nebraska, North Dakota, South Dakota and Wisconsin (the Plains Commonwealth and Midwest Commonwealth).
In California, it is said that there are miles wide twisters in the Midwest, and that the place is one big radioactive dustbowl.
One of the major factions in the area is the Brotherhood of Steel, a splinter faction of the original Brotherhood from California that controlled the area around Chicago. The technology-worshipping Reaver cult, based in Newton is also a notable organization.
Some of the major towns were Quincy, with both human and ghoul population, Kansas City, inhabited by ghouls who worshipped a nuclear bomb, the Junktown-like Junction City, Coldwater, famous for its casino and Great Bend, a major pre-War industry center. A dying town of Macomb and numerous small settlements and tribes (like Peoria, Brahmin Wood and Dirt Haven) are located here as well.
After the fall of the Master in the far West, a great migration of super mutants he created began. They traveled East to find themselves a new home, until they found a crashed Brotherhood of Steel zeppelin, which was a part of an Air Convoy that was meant to find and destroy the remains of Master's Army. Brotherhood Paladin Latham duelled mutant leader Gammorin and won. As unlikely it may seem, Latham took his opponent's name and became the new leader of the mutant army, setting up the base known as Osceolla near the airship crash site.
Long faction war occurred in this region, as the local Brotherhood were fighting Super Mutants, Beastlords, raiders and Reavers. Also, Vault 0 and the Calculator were located in the Midwest, arising as the greatest threat to all life and the main enemy of the Brotherhood.
Caesar's Legion pack encountered in Denver travels to the east (in the direction of Kansas), where its new headquarter is located. The Legion pack appears there once a year. Then every couple of weeks a pair of fast guys scout out east, if the radioactive dust storms have subsided for the season. Once they do, they'll head out. Once the Legion pack is discovered in Denver, every month that passes has a 25% chance, that Legion slavers left to go back to Caesar taking all their slaves with them.