The story of Prey 2 focuses on U.S. Marshal Killian Samuels, who starts the game on a passenger flight which suddenly crashes onto the Sphere (the crash is shown in the original Prey). At the end of a short battle with some aliens he is knocked unconscious, after which the plot jumps forward several years. Samuels is now a bounty hunter on the alien world Exodus. Though he is aware of his profession and has retained his skills, he has no memory of what happened in the time that passed since his abduction. He initially believes himself to be the only human on Exodus until he runs into Domasi "Tommy" Tawodi (the protagonist of the original Prey), whom he has apparently met in the period he no longer remembers. Killian then resumes his bounty hunter activities while recovering his memory.

CPU: Intel Core2 Duo 2.2GHz or AMD Athlon 64 X2 5000+ 2.6GHz
RAM: 1.5 GB for Windows XP or 2 GB for Windows Vista and Windows 7
HDD: 10.5 GB free disk space
Graphics: 512 MB Graphics Memory
Sound Card: DirectX 9 Compatible
DirectX: Version 9