In essence, the story revolves around two separate events happening simultaneously. On one hand, scientists discover a fossil of Mew's eyelash and extract its DNA to create Mewtwo, a legendary Pokémon with immense power and immortality. However, soon after its birth, Mewtwo turns against humanity in search of its purpose in existence. On the other hand, Satoshi, Kasumi, and Takeshi receive an invitation from an unknown source to meet the greatest Pokémon trainer at New Island Castle. Upon their arrival, they encounter three other trainers as well as their mysterious host, who turns out to be Mewtwo. The creature challenges its guests with clones of its own, testing their skills as trainers.
Mewtwo no Gyakushuu Evolution was published in English as Pokémon: Mewtwo Strikes Back - Evolution by VIZ Media on August 11, 2020.