In the game's primary player versus environment game modes, players join a four-person team of post-apocalypse survivors called Cleaners, who must fight their way through levels populated by zombie-like monsters called The Ridden. Teammates are either controlled by other players or AI bots depending on matchmaking preferences and player availability.[2] A new feature of Back 4 Blood is cards. At the start of each level, players need to build their deck with cards that adjust various elements of gameplay, such as modifying the player's health, damage, and stamina. Along with player cards, the AI Director will also use Corruption cards against the player to hinder their progress. The AI can spawn extra enemies, activate a fog effect, and increase the size of the horde.[4] The game features pre-defined hero characters who have preset attributes and abilities, and players can purchase upgrades and items with an in-game currency called Copper.
The game has an eight-person player versus player mode called Swarm, where a team of four players assumes the role of Cleaners, and the other team of four control mutated Ridden. The teams are tasked with eliminating one another within a closed area.