Mew, a Pokémon of myth, is believed to possess unparalleled abilities and an immortal life. Scientists endeavor to create the strongest Pokémon in the world and extract DNA from a fossil containing one of Mew's eyelashes, giving birth to the Legendary Pokémon known as Mewtwo. The monster violently destroys the laboratory soon after its emergence, and sets forth to seek retribution against humanity, driven by the search for its own purpose.
In the meantime, Satoshi, Kasumi, and Takeshi receive an enigmatic invitation to a castle on New Island, where they can meet the greatest Pokémon trainer of all time. Eager to embark on this journey, Satoshi agrees to accept the invitation. Upon arriving at the castle, the group encounters three other trainers that were also called for their potential: Sorao, Umio, and Sweet. Little does anyone know, their host and the trainer they all have been waiting for is Mewtwo itself, who challenges the guests with clone Pokémon of their own!