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In Doom RPG, the doom marine returns to mars, where the player is sent to assist the UAC mars outpost, which is under attack by demons. The player must visit seven infested sectors of the base encountering scientists such as Dr. Guerard, Dr. Kelvin, Mr. Narida, and Dr. Jensen. Throughout the game, you learn of a scientist named Kronos who worked on teleportation, was fired by the UAC, and was the cause of the demonic invasion. Eventually the player learns that Kronos is still in the base.

Dr. Guerard begins giving the player instructions. In sector 3, Mr. Nadira lures the player into a trap. The other scientists begin to express their distrust of Guerard and in Sector 6, it is revealed that Nadira and Guerard are working together. Guerard double-crosses Nadira, allowing a demon to kill him. A second attack almost completely destroys the base, but Dr. Kelvin is able to open the reactor door. The doom marine confronts Dr. Guerard, who is actually Kronos and transforms into a demon. After Kronos is killed, the player fights through demons to shut off power to the reactor, stopping the demonic invasion.

Just before the portal closes, a Cyberdemon leaps through the portal. The player must defeat the cyberdemon to finish the game. Afterwards, the player is returned to a "repaired" junction where they can complete all objectives of the game.