Abomination plays similar to squad-based strategy games such as the X-COM series or Incubation. The player is in charge of preventing the city in which the game takes place from being overrun by fanatic cultists and mutants. Similar to X-COM, the game takes place on two separate strategy screens. The first is the tactical city map lets you manage your heroes, the squad, and examine the city for incidents which call for your attention. The second are the randomly generated missions that take place in an isometric city tile set, similar to X-COM. Though the plot is the same each time, the generated missions vary each playthrough.
With limited variation in the mission types, the most common means of victory is to kill all the cultists and mutants present on a mission. Missions are played out in a pausable real-time manner in which the player is allowed to pause an issue orders that the AI will attempt to execute upon resuming.