It's been several years since the battle of Groudon and Kyogre wrought havoc on the Hoenn region. Humanity's understanding of Pokémon has deepened as more discoveries are made about the origins of Pokémon. A recent surge of discoveries in the nearby Issho region has drawn researchers from all over the world, including May, now an assistant Pokémon professor. After receiving a Pokémon from her, the player sets out to investigate the reports coming from all over the Issho region of new species of Pokémon, new types of Pokémon, and even more strange phenomena. Meanwhile, a new threat is on the rise in Issho, a mysterious crime syndicate who use exceptionally powerful Pokémon.