Aliens vs. Predator: Requiem is a third-person action-adventure game. The single-player campaign is composed of 15 missions and features the Predator from the film. The player has access to Predator weapons as seen in movies and other sources in the franchise, including claws and a shoulder-mounted energy cannon. New weapons from the corresponding film include an energy pistol.
The player character also has stealth camouflage and several vision modes that allow him to see in the dark, such as infrared vision. Health is represented by a segmented life bar that regenerates after a successful kill, and an energy bar is also available to provide power for the Predator's weapons. In addition to destroying Aliens, the Predator must eradicate other traces of their presence, including facehugger husks. Aliens, husks, humans, and other potential targets are all represented by icons on a heads-up display. The game's camera is manipulated by pressing the PlayStation Portable (PSP)'s triggers, and the Predator can "lock on" to opponents using a first-person view to target them with his ranged weapons.

Aliens vs. Predator: Requiem uses a system of "honor points" to award points to players for actions considered honorable for Predators. For instance, "tagging" an enemy in first-person mode before killing it adds points, while killing humans reduces points. Honor points are used at the end of each mission to upgrade the Predator's weapons and equipment. In addition to the campaign, a single-player mode called "Skirmish" is available,[3] in which players have five minutes to dispose of as many Aliens as possible in one of the game's maps. Skirmish can also be played in a cooperative setting with one other player using the PSP's "ad-hoc" local wireless mode.