The player has to get through each level, from start to finish, by slaughtering countless monsters. The game is divided into several chapters, each with several levels. Each level presents a new location with various themes and includes castles, monasteries, graveyards, and more. Several classic weapons will be returning including the Painkiller, the stakethrower, the shotgun, and the electrodriver, however, new guns will also be available such as the Soulcatcher, a.k.a. the Small Sucking Gun, which shoots saw blades in primary firing mode and sucks the souls out of the enemies with its secondary firing.
Painkiller: Hell & Damnation will also add several multiplayer modes to the series. The entire single-player campaign can be played by two people and the level of difficulty adjusts in accordance with the 2 players, either through the number of enemies or the amount of hit points. In survival mode, up to eight players battle for survival in a limited area of one map. Endless waves of enemy hordes will attack the player or players. Other player vs player based game modes include deathmatch, team deathmatch, capture the flag and duels.