Manhunt 2 takes place in the Dixmor Insane Asylum, where patients are subjected to cruel treatment rather than medical care. A power outage allows them to revolt, leading to chaos and mayhem. The player controls Dr. Daniel Lamb and Leo Kasper, switching between the two characters throughout the game.
The gameplay is largely stealth-based, with an emphasis on cover and strategy. As players progress, they'll encounter more firearms and need to use these to take down enemies. A radar system helps track enemy movements, and kills are often performed from the shadows. Players can also use objects or the USB headset to distract or lure enemies away.
One of the game's most notorious features is its execution mechanic, which allows players to perform various kills on enemies. These executions are bloody and graphic, but some are censored due to content restrictions. The Wii version introduces a new control mechanism, where players must mimic the motions needed for a kill using the Wiimote and Nunchuk.
All versions of Manhunt 2 share similar gameplay mechanics, with some minor differences between them. The Wii edition includes exclusive weapons and additional features, such as a short tutorial and more detailed environments. However, these changes are relatively minor compared to the game's overall design and mechanics.