Bayou City is the primary setting of The House of the Dead: Overkill. A small city located in Bayou County, Louisiana, it was hit with a mutant outbreak caused by discovered samples of the mutagen Formula X.
- Sugar Plantation - A large-scale, estate privately owned by Papa Caesar supposedly used for farming cash crops. In truth, the plantation was among one of Caesar's fronts used to refine Formula X, housing a small laboratory underneath used by Jasper Guns.
- Pink Pussycat - A local strip club where Varla Guns and Candi Stryper worked.
- Save-O-Rama - A local mini market.
- PetroFun - A local gas station.
- Mort's Saloon - A local bar frequented by bikers.
- Bayou County General - Bayou City's local hospital. It too serves as one of Caesar's fronts, housing dangerous mutants, such as the Screamer.
- Mulholland Bros' Carnival of Fun - Located in the outskirts of Bayou City. It is a fairly large carnival consisting of various minigames, arcades, rides, and a "freak show" attraction. In addition, the carnival also has a football field used by a football team, the Roosters.
- Tasty Cattle Co. - A large slaughterhouse located in the outskirts of Bayou City. Caesar used the facility's cold storage to house numerous mutants.
- Train Station - Bayou City's railway facility.
- Bayou County's swamp is home to small wildlife, such as birds and rats. Due to the outbreak of Formula X, the local wildlife and rural residence living within the swamp have been turned into hostile mutants. Its murky water is also home to the Lobber.
- Bayou County Correctional Facility - Located 500 yards from the swamp. It is a large prison, formerly a hidden military complex that housed Formula X.
- In real-life, Bayou County would be an inaccurate term used for the region as the territories within the state of Lousiana are termed as parishes, which are equivalent to counties.