In response to the mysterious disappearances of four ninjas, each with a distinct bloodline limit, from different nations, Kakashi Hatake, Naruto Uzumaki, Sakura Haruno, and Sai embark on a mission to investigate. Upon finding these missing ninjas and reporting their findings to the Hokage, Tsunade, their plans are abruptly interrupted when Hiruko, a former Konohagakure shinobi driven by an insatiable desire for power, surfaces. He has assimilated the unique abilities of the vanished ninjas, rendering him nearly invincible, and he is just one more bloodline limit away from starting a global conquest.
Konohagakure faces suspicion from other nations due to its historical connection with Hiruko, leading to Tsunade receiving an ultimatum to address the situation. With limited options, Tsunade agrees to a risky and potentially fatal strategy suggested by Kakashi. Naruto, however, is unwilling to let this plan proceed, defying the Hokage's order and vowing to save Kakashi, ready to confront both friends and foes in the process.