Up to Chapter 5 of Derek’s missions, much of the story remains the same as the DS version, though the Wii version’s Chapter 6 assumes the DS version’s had already taken place. As Derek’s story’s progresses, Nozomi’s missions are unlocked. During her missions, it is revealed that she was working for Delphi, who knew of her ability and was using it for their own purposes. Nozomi remains mostly unaware of the circumstances of Delphi until just before their raid, and also places their operation in danger at one point by insisting on operating on a reporter wounded after chasing down a car in which Nozomi and a Delphi operative were passengers. Just before their headquarters are discovered by Caduceus, Nozomi escapes with a GUILT sample which she plans to use as a bargaining chip.
After Derek’s Chapter 5 and Naomi’s missions are cleared, Chapter 6 is unlocked. The plot of the chapter takes place at Caduceus Europe, where Derek and Angie have been invited to provide assistance and Dr. Hoffman has come to attend a conference held under near-total secrecy. There, Derek meets Naomi for the first time, who is now using her original name of “Dr. Kimishima” and granted amnesty in Europe, along with another doctor called Owen. Dr. Miller tells Derek about the Z-Cells, which are fruit of their research on GUILT in order to find a way to use it to help people.
After Derek eliminates a somewhat stronger strain of Tetarti, his heart becomes infected with a combination of Kyriaki and Paraskevi, which leaves Naomi to heal Derek. Angie volunteered to assist Dr. Kimishima, but at certain moments was unable to see Derek in the condition he was in, crying many times and jumping to severe conclusions. Naomi succeeds, and time passes, during which, Angie described her true feelings to Derek. During the scheduled conference where Dr. Owen explains how a patient has recovered from a wound after a Z-Cell injection, Naomi expresses her doubts, claiming that GUILT was created to kill people, and probably could never be used to save them. Soon after the patient suffers from an injury that causes his blood to spray all over the conference room, infecting all the attendees with various strains of GUILT.
After Derek and Naomi deal with the infected attendees, Owen tries to escape and reveals that he was working all this time for Delphi. Dr. Miller orders him to be stripped of his rank and taken away, and is then told that there is a problem in the lab where Adam is kept. Meanwhile, at the lab, Derek learns that the Z-Cells are taken from Adam himself, and that Hoffman has become infected with a strain of GUILT that is revealed to be a stronger version of Savato. In the final mission of the game, Derek and Naomi work together to take down the upgraded Savato and save Hoffman’s life.
Afterwards, Caduceus International proposes a treaty to deal with GUILT research which is quickly ratified. As for Derek and Angie, they are revealed to be assigned to northern Afghanistan, but not much else is revealed in the main game – though Tyler Chase, talking to Leslie Sears and Stephen Clarks, claims that both Derek and Angie deserve a long holiday because lately, they did not have much time to spend together alone… Naomi reveals that she cannot leave Europe without facing criminal charges for her work with Delphi, and parts ways with Derek.
A series of special levels can be played at this point where either, Derek or Naomi is operating on Adam, the leader of Delphi, to remove the last of the surviving GUILT strands within him, to destroy the virus once and for all.
