Mewtwo fights with a Tyranitar and two Escavalier in a mountain range. It escapes but is badly injured, while the Tyranitar and Escavalier are swept away by a landslide caused by their fighting.
Sometime later, Virgil is on his way back to base with his Eevee after completing another rescue mission. His helicopter has engine trouble, forcing him to land for repairs. He meets Anna and her grandfather Oscar, who live in a cabin in the mountains. While talking with Virgil after giving him some lunch, they explain their encounter with a Pokémon whose identity was unknown to them. Some time prior, they had been hiking with their Stoutland when all three of them fell into a deep crevasse. The Pokémon—Mewtwo, unbeknownst to them—saved them with its Psychic before flying away.
Having overheard their conversation, a man with his right arm in a sling approaches them. He introduces himself as Dirk and reveals Mewtwo's identity, explaining that Mewtwo saved him from a landslide but it and his Escavalier were caught up in the disaster. Virgil mobilizes his Team Eevee to aid Dirk in recovering his Pokémon, a mission they successfully accomplish. However, Dirk expresses worry that Mewtwo is badly injured as well, and asks Virgil, Anna, and Oscar to help him find it.
Meanwhile, Mewtwo soaks in an underwater spring to recover. A Marill and Azumarill swim up to it, but flee when it glares at them.
Virgil, Anna, and Oscar examine a map of the region and realize that finding Mewtwo will be difficult. Virgil suggests that he can use his helicopter to search from the air, but Dirk says that Mewtwo will be frightened away due to its distrust in humans. When pressed on how he knows so much about Mewtwo, Dirk confesses that Mewtwo was created by humans using the genes of Mew. When it became the subject of cruel experiments, Mewtwo escaped the laboratory. Dirk says that he was searching for Mewtwo to offer it protection, but when he finally found it, they were caught in the landslide.
Virgil sends Team Eevee out to search for Mewtwo alongside Stoutland, and Anna uses her ability to connect with the hearts of the forest Pokémon to get their aid as well. Virgil's Eevee, Vaporeon, and Leafeon encounter the Marill and Azumarill from earlier and learn of Mewtwo's location. However, they are unaware that a camera drone is following them, recording a feed that Dirk is secretly monitoring on his wrist device. Dirk slips off on his own while the others are not looking.
Team Eevee reunites with Stoutland at the cave Mewtwo occupies, and Eevee, Espeon, and Stoutland bring a Revival Herb to Mewtwo. Mewtwo, however, refuses all aid. As they leave the cave, Dirk is standing on a cliff overlooking the clearing. He removes his sling and summons an army of robotic drones to surround the clearing and cave entrance. Angered by the disturbance, Mewtwo attempts to leave, only to be trapped by the electromagnetic barrier generated by the drones and attacked by Dirk's Tyranitar and Escavalier. When seemingly cornered, Mewtwo Mega Evolves into Mega Mewtwo Y and counterattacks using its incredible speed.
Virgil, Anna, and Oscar arrive, discover the scene, and confront Dirk. Dirk claims to not have lied about his goals, saying instead that he simply failed to tell them that he is a Pokémon poacher hired by Mewtwo's creators to recapture it. Mewtwo says that it knew humans could not be trusted before resuming the battle. Anna apologizes to Mewtwo, saying that she did not know the truth about Dirk.
Suddenly, after having been hit by Tyranitar's Hyper Beam earlier, some of Dirk's drones spark and cause a forest fire. Virgil calls Team Eevee forth, but the flames quickly surround them. The drones surround Mewtwo and begin attacking it. Within moments, Mewtwo is restrained by energy blasts fired from the drones, but it frees itself using Psystrike. Mewtwo then dodges several more blasts and Mega Evolves, destroying the drones using its speed and psychic powers. Several of the burning drones crash around Dirk, causing him to fall down the cliff and drop his Poké Balls.
Flying over the forest, Mewtwo muses that it was created to be the strongest Pokémon, but everyone who gets involved with it only finds trouble. It uses Psychic to lift all the water from a nearby lake and drop it onto the fire, extinguishing the flames.
Dirk awakens and calls for Tyranitar and the Escavalier to attack Mewtwo again, only for Mewtwo to crush the Poké Balls with Psychic. Tyranitar and the two Escavalier walk off, freed from Dirk's control. With no other options, Dirk begs Mewtwo for mercy, saying that he only attacked it because the scientists told him to. Virgil's Espeon and Umbreon use Psychic to lift up and capture Dirk, and Virgil says that he will take Dirk to Officer Jenny. Virgil, Anna, and Oscar all thank Mewtwo for saving them, but it says that it was merely helping the Pokémon. Mewtwo asks them to forget their meeting and then flies away into a thunderstorm, asking itself if it will ever find a place to call home.
At a Pokémon Center, Ash, Iris, and Cilan are speaking to Professor Oak, who tells them to visit a park called Pokémon Hills in New Tork City where his friend works. Iris turns around and sees Virgil in an interview on television. The interviewer asks him what is important for the Pokémon Rescue Squad, and Virgil looks up to the sky. Thinking of Mewtwo, he answers that it is all about people and Pokémon connecting to each other with open hearts.