Two years have passed. During an expedition to the planet Aegis VII, of scientists discover a giant specimen of Necromorph, trapped in the ice, the Nexus. They extract a sample of specimens for study. Isaac Clarke at form a new team, with Ellie Langford, Emily Simmons, Mathias Bagans and Calista Ox. One day, they are sent on the planet Aegis VII, because in recent weeks, the research station Thanatos, unresponsive. On the place, the team discovers that the Necromorph virus, has spread throughout the base and has contaminated throughout the staff, turning them into rabid Necromorphs. And they will discover that the unitologists are also involved. For the soldiers, the nightmare begins again and the fight for survival also.

In 2520, the humans have colonized space and built a city floating in the space with powerful nuclear reactors: Space town. But recently, the city does not respond, it's the radio silence. A team of elite soldiers, led by Isaac Clarke, a strong man and great warrior, is sent out to find out what happens. When they got, they discover that the city has become the battlefield between the humans and a monstrous race of aliens, the Necromorphs. Helped by Ellie Langford, the woman who runs the resistance, Isaac will try to understand why the Necromorphs attacked this city and he will also discover that the real monsters are not the ones he thinks.