Commander Keen - Doom of Mars is a thrilling crossover game combining elements from Commander Keen and Doom. After overcoming Mortimer McMire's robot army, Commander Keen embarks on a journey to Mars. The Vorticons, Martians, and Gnosticenes have collaborated to create a teleporter system for interplanetary travel, aiming for peace among their species.

Keen arrives at Mars to discover three teleporter stations for testing purposes, one on Mars itself and the others on its moons Phobos and Deimos. As he ventures through the Mars Lab, unexpected events unfold—electricity disruptions, explosions, and a malfunctioning communication system. Keen must race against time to reach the teleporter room, shutting down the system to prevent a catastrophic facility explosion.