On Sunday May 1, 2146, an orbital probe recorded a faint unidentified signal broadcast from the abandoned Mars Site 1 complex. Months later, on Monday August 8, 2146, the UAC board of directors announced the renewal of the Mars program, now led by Dr. Elizabeth McNeil, a ex-colleague of Betruger, who had transferred off Mars days before the outbreak and was the original one who requested Councilor Swann's presence on Mars. McNeil's main objective was to continue the experiments on Mars and discover what Betruger unleashed.
Once more, strange occurrences haunt the facility. The player now takes control of a combat engineer marine, he is older than the original Doom 3's protagonist.