Prey is a single-player first-person, horror, action, and role-playing game. The story takes place aboard Talos I, a massive space station orbiting the moon in an alternate history where advanced technology has reshaped human progress. The player assumes the role of Morgan Yu, a scientist caught in an experiment gone wrong, who awakens to find the station overrun by an alien species known as the Typhon. Morgan must survive, uncover the truth of past choices, and determine the fate of both the station and humanity itself.

The core gameplay combines exploration, combat, and resource management within the interconnected areas of Talos I. The player navigates offices, laboratories, and maintenance tunnels, often using keycards, hacking skills, or alternative pathways to progress. Combat features both conventional weapons, such as pistols and shotguns, and experimental tools like the GLOO Cannon, which can immobilize enemies or create climbable surfaces. Encounters with Typhon enemies vary from small shape-shifting Mimics to larger psychic creatures that require tactical approaches.

Progression is handled through Neuromods, devices that unlock new abilities for Morgan. These include human-based upgrades, such as improved stamina and hacking proficiency, as well as Typhon-derived powers that grant telekinetic or energy-based abilities. Players must decide how much to embrace alien powers, as this choice affects access to certain tools and alters how automated defense systems respond. Inventory management requires careful balancing of ammunition, crafting materials, and health-restoring items, with crafting stations allowing the recycling of found objects into usable supplies.

Beyond direct combat, survival depends on creative problem-solving. Environmental hazards like fires, radiation, and decompression can be navigated with the right equipment or ingenuity. Zero-gravity traversal in space segments expands exploration beyond the station itself, requiring oxygen management and situational awareness. Stealth offers another option, as players can avoid powerful Typhon instead of engaging them directly.

Multiple-choice dialogue and branching quests shape alliances with survivors aboard Talos I, and decisions influence different story outcomes. Terminals, emails, and audio logs provide background on the crew and the station. The game also features a morality component, as actions such as saving or sacrificing individuals weigh into the narrative conclusion.