After the assassination of President Johnson, the Colonel asks Raiden to honor his last directive—to rescue computer programmer Emma Emmerich, step-sister of Otacon, and help her upload a virus into Arsenal Gear’s AI system, GW. On the way to the flooded Shell 2 core where she is trapped, Raiden encounters Vamp again, who survived bullet wounds to the forehead and abdomen. Vamp reveals that even without the possibility of a nuclear strike, they could still use Arsenal's purified hydrogen bomb to emit an EMP over Manhattan, knocking it offline. He also hints that, contrary to what the press stated, Dead Cell was actually framed for the terrorist acts six months prior by the Patriots. Raiden is then forced to fight and defeat Vamp before pressing on to rescue Emma.

After finding Emma, Raiden struggles to convince her to accompany him. Not only is she suspicious that he is with the terrorists, but due to a near-death experience when she was a child, in which she nearly drowned, she is afraid to swim out of the flooded core. With patience, Raiden convinces her to hold on to him as he helps her escape. Along the way, Emma explains that she created the GW AI that controls Arsenal Gear. Together, the two then head to the Shell 1 core to upload the virus, but Vamp appears again and stabs Emma before being shot by Raiden. Emma uploads the virus but dies from her injury as the virus is cut off prematurely. Otacon leads the rescue of the remaining hostages while Raiden is captured by the Cyborg Ninja, who is revealed to be Olga Gurluchovich, and Snake seemingly betrays him as well. Big Shell then collapses as Arsenal departs.