In this narrative-driven, third-person survival horror game set 300 years in the future, the player will take on the role of Jacob Lee – a victim of fate thrown into Black Iron Prison, a maximum-security penitentiary located on Jupiter's moon, Callisto. When inmates begin to transform into monstrous creatures, the prison is thrown into chaos.

Set on Jupiter’s dead moon Callisto in the year 2320, The Callisto Protocol casts players as Jacob Lee, an inmate in Black Iron Prison. When a mysterious outbreak throws the moon into chaos, Jacob must face his darkest fears to defeat the bloodthirsty creatures that stalk him as he unravels the dark mysteries at the heart of the powerful United Jupiter Company.