Painkiller: Hell & Damnation is an enhanced remake based on the original Painkiller and the expansion Painkiller: Battle Out of Hell. Of the 34 levels originally available in those games, 14 are featured in this title reorganized in four chapters. Each chapter has a boss and they were reconstructed with changes to the level design and the enemies. There is also a global graphical overhaul courtesy of converting the game from the original PAIN engine to Unreal Engine 3. Most of the visual enhancements are apparent in the character models and skins. It is the second time a game in the series is available for consoles, following the 2006 Xbox title Painkiller: Hell Wars.

The game starts with a new intro cinematic that changes the setup of Daniel Garner's trip to purgatory. Next to the original weapons the Soulcatcher is introduced. It combines a saw blade with an energy beam to suck up the souls of defeated enemies right away. The original music is complemented by some new tracks by Ojo Rojo. Entirely new is a cooperative mode, both local and online, where the protagonist Daniel Garner can team up with Eve to tackle the levels together. It also introduces a survival mode where up to eight players can fight together to survive waves of enemies. The original PvP multiplayer modes are still present and the game is described as uncut with none of the gore or blood removed.