Up to four players must survive endless waves of attacking Zombies, earning points from killing zombies and repairing defenses. These points may be used to purchase weapons and perks in the process, or to unlock new areas and activate other special objects. Zombies enter the player-accessible area of the map via windows, holes in walls, or climbing out of a "dirt" surface, which are initially barricaded but will be rapidly demolished by zombies. They can be repaired, however, with the exception of the dirt surfaces. There is no limit to the number of rounds; the game will end when all players have been incapacitated or killed by the zombies. Zombies become stronger and faster upon the completion of each round, forcing players to make tactical decisions about point spending and progressing through the map. On occasion, zombies will drop power-ups such as Max Ammo, Nuke, Insta-kill, or Carpenter (Shino Numa and Der Riese only) upon their death, making the round easier.
Altogether, Nazi Zombies consists of four maps; Nacht der Untoten (night of the undead), Verrückt (crazily), Shi No Numa (zombie swamp), and Der Riese (the giant).