Manhunt 2 takes place in the Dixmor Insane Asylum, where patients are subjected to brutal treatment. A power outage sparks chaos, and the player must navigate through the asylum and other locations as either Dr. Daniel Lamb or Leo Kasper.
All versions share similarities, but the Wii edition includes exclusive weapons like a bottle, mace, and razor. Other versions feature additional content such as a samurai sword and tutorial in the Wii version. The Wii edition also boasts more detailed environments, additional dialogue, new hunters, and enhanced animations for character interactions.