Mewtwo was intended to be the most fearsome Pokemon in Pokemon Red & Blue, but all challenge was taken away by the presence of the Master Ball. A Dungeons & Dragons party will have no such luck if they run afoul of Mewtwo in some mysterious dungeon.
Mewtwo was the product of bizarre gene-splicing experiments performed on the DNA of a Pokemon named Mew. It was easily the most powerful Pokemon in Pokemon Red & Blue, and it existed as one final challenge/reward for the players who managed to defeat the Champion. Mewtwo has remained one of the most powerful Pokemon in the series, and only a handful of creatures have ever come close to its strength.
Setting The Scene - The Abomination
Mewtwo was created using advanced technology, but it's easy to substitute the same processes for alchemical or magic in a D&D world. The players should learn about Mewtwo's existence long before they meet it, through journals or reports written by its creators. It's possible that they find the abandoned laboratory where Mewtwo was created, which is now in disrepair and crawling with abominations.
It's important to determine a motive for the players to tackle Mewtwo. In the video games, Mewtwo is just minding its own business in the Cerulean Cave. It's possible that the Mewtwo encounter could be saved for a post-storyline battle, ala the Weapon monsters in the Final Fantasy series. The notes left by Mewtwo's creators could establish that it's a ticking time bomb and that its psychic powers will one day be unleashed in a wave that could kill countless possible. Maybe the party learns that Mewtwo is training its psychic abilities in secret so that it can one day unleash them upon the world and punish the human/demihuman races that were responsible for creating it.
Mewtwo can be found deep within its lair, which is a pitch-black cave that is filled with underground streams. The psychic powers possessed by Mewtwo will allow it to ensnare the minds of lesser creatures so that they can be used as guardians for its home. The party should have a difficult time navigating the cave, which should be crawling with charmed monsters. Mewtwo's powers are such that it should be aware of the party's presence as soon as they enter its lair, but it will monitor them using magic spells before deciding how and when to engage them in combat.
Mewtwo's Stats
Strategies & Tactics
Mewtwo is a high-level psychic threat. Once it becomes aware that intruders are closing in, it will prepare illusions in order to hide its current position. Mewtwo favors mind control spells and will use them to turn party members against each other. Once Mewtwo identifies the spellcasters in the group, it will engage them in melee range in order to use Pressure on them. For its Legendary Actions, Mewtwo will open the battle with Psychic and will favor this move for as long as it avoids taking damage. Mewtwo will use Barrier to try and limit the party's movements if they try to surround it. If Mewtwo is badly wounded, it will attempt to Teleport out of sight and use its Recover move to keep healing while the party looks for it. Mewtwo's regenerative abilities should be described in great detail to the party, as it seemingly heals instantly from wounds.
If Mewtwo feels that it's overmatched, it will attempt to flee, using illusion spells to cover its tracks or teleportation spells for a snap escape. As a high-level spellcaster foe, Mewtwo will show no mercy to anyone who enters its lair. Mewtwo has no problem using charm/domination spells to force the party to turn on each other. The party will have an incredibly difficult battle ahead of them, and even spells like Mind Blank will only offer them so much protection against the might of Mewtwo.