Isaac Clarke was explaining to the doctors about the incident at Ishimura. Half the scientists are killed by the Unitologists led by Daina le Guin. They try to capture Isaac,but he quickly escapes. He runs into Nolan Stross,who tells him about the new Marker and was about to be given to Hans Tiedemann,director of EarthGov. Isaac meets Ellie Langford and they investigate together.
The Unitologist leader,Jacob Danik orders Daina to find Isaac before he gets to the new Marker. Later,They are attacked by Necromorphs. EarthGov open fire at them and captures Isaac,Daina,and Nolan. They see that the Necromorph are behind the glass. Tiedemann tells Clarke that ever since Kendra Daniels fails to deliver the Marker,EarthGov came up with a better plan about the new Marker.
The Unitologists infiltrates the base. Stross helps Isaac and Ellie escape and was killed by Daina,who was then killed by Tiedemann as the Marker activates. Isaac manage to stop it and causes the base to trigger the self-destruct ignition. Tiedemann tries to kill Clarke,but Ellie broke the glass and freeing the Necromorphs,who kills him. Isaac and Ellie flies to the ship as the base exploded.
They return to earth where Isaac explains the situation. As the sun begin to set,Isaac and Ellie had a feeling that their troubles are far from over.