In 2014, Naomi sends Otacon and Snake a video message claiming to have been kidnapped by Liquid Ocelot in order to hijack the SOP System. In reality, she is working with him in order to destroy the Patriots' AI. Snake finds her in South America, and she discovers the cause of Snake's accelerated aging, as well as informing him that Foxdie would cause an epidemic due to his genetic mutation.
She also found the second strain of Foxdie within him, which, unbeknownst to them, was injected by the Patriots via Drebin to kill Eva, Ocelot, and Big Boss. Naomi accompanies them to Eastern Europe. Aboard the Nomad she forms a bond with Sunny, the daughter of Olga Gurlukovitch, and becomes romantically involved with Otacon. She even felt a deep sympathy for Raiden, who became the next Cyborg Ninja, succeeding her foster brother and Sunny's mother. She creates 2/3 of the program that destroys GW and leaves the last part of the new program, FOXALIVE, to be finished by Sunny.
She escapes the Nomad and returns to Liquid, letting the others believe her a traitor. After Vamp's death, she reveals she had been diagnosed with terminal cancer, kept in check through the use of nanomachines. She dies shortly afterward by suppressing said nanomachines. In the debriefing, Naked Son, it is revealed that she had been working with Ocelot and Eva, and that the three of them planned "Liquid's" uprising in advance. Naomi wanted to stop the Patriots and revive Big Boss, whom she loved along with Gray Fox. She left him a message telling about the plan, as well as the results of further research she did, explaining that the second strain of Foxdie stopped the old strain from mutating, meaning Snake would not have to commit suicide.
