- Modest (only for Mewtwo and Mega Mewtwo Y)
- Adamant (only for Mega Mewtwo X)
- Timid (only for Mewtwo and Mega Mewtwo Y)
- Jolly (only for Mega Mewtwo X)
Note: The Natures above are Natures for sweeper Mewtwo, not bulky Mewtwo.
If your Mewtwo Mega Evolves into Mega Mewtwo X and is mixed (has Attack and Special Attack EVs) like mine (my Mewtwo has Psystrike and three Physical moves), then I suggest you give it a Naive Nature/Modest Nature (Mega Mewtwo X has ridiculously high Attack, so it can be lowered a little with the Modest Nature)