In a world with an alternate history, a great war finally comes to an end leaving the earth diseased and polluted. The geneticist Dr. Azuma vies for support from the government for his neo-cell treatment that he claims can rejuvenate the body and regenerate humankind. The government leaders, guarding their own deeply entrenched powers, turn down the professor. Driven to complete his work, Dr. Azuma accepts a secret offer from a sinister faction of the powerful military. After an incident occurs in Dr. Azuma's lab, a race of mutant humans known as the Shinzo Ningen are unleashed upon the world. Now only the warrior known as Casshern, reincarnated with an invincible body, stands between the Shinzo Ningen and a world on the brink of annihilation.

High school student Ling Xiaoyu is recruited by Anna Williams of G Corporation to transfer to Kyoto University and gather information on a student named Shin Kamiya. Meanwhile, Jin Kazama, the current head of the Mishima Zaibatsu, sends Alisa Bosconovitch to the university for the same mission. Though they do not know each other's true motives, Xiaoyu and Alisa become close friends. However, their friendship is put to the test when Shin is captured by an unknown assailant.