|The following is based on Fallout Tactics and some details might contradict canon.|
In the old times, St. Louis was a big city that was mostly destroyed during the Great War.
Around 2197, the Eastern Brotherhood of Steel's Fang Squad encountered a large contingent of heavily armed super mutants in the region of St. Louis. They fought bravely against this overwhelming force and managed to radio in a distress call right before they were annihilated. Eight battle-hardened squads led by General Simon Barnaky rushed to the scene and engaged in pitched combat with the super mutants. While the Brotherhood was able to push them back initially, its losses were staggering. As a result, they needed to pull their forces out of there. At General Barnaky's request, the squad led by the one later known as the Warrior was sent to rendezvous with his mobile command center and execute the evacuation of the wounded Brothers. There were three groups to be evacuated, including the one led by General Barnaky, but only one, led by Paladin Emerald Solo was evacuated. All others were killed, with only Barnaky, who was taken prisoner by the super mutant High Inquisitor Toccamatta, and Burke, who lived long enough to meet the Warrior, survived the slaughter.
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The mission in St. Louis is to find and evacuate three Brotherhood squads that were either wounded or went missing in action.