After saving the life of their heir apparent, tenacious loner Snake Eyes is welcomed into an ancient Japanese clan called the Arashikage where he is taught the ways of the ninja warrior. But, when secrets from his past are revealed, Snake Eyes' honor and allegiance will be tested – even if that means losing the trust of those closest to him.

Set 15 years after "Twentieth Century Boys," Kanna (Airi Taira) reunites with several main characters from the first film in an attempt to stop Friend's increasing influence over the world and continued plans to eliminate humanity, as detailed in the New Book of Prophecy.