When Middleton High School participates in a student exchange program, Ron is selected to go to a school in Japan while a student named Hirotaka is chosen to come to Middleton. Ron finds out that the school he was assigned to visit is a secret ninja school while Kim and Monique eventually start crushing on Hirotaka. However, when Lord Monkey Fist steals the Lotus Blade from Ron’s sensei, it’s up to Ron to save the day; though without Kim’s help.

Yori’s sensei has been kidnapped and all evidence indicates that Lord Monkey Fist is responsible for it. Yori comes to Middleton to get Ron, in which Yori and Ron head off to South America to attempt to stop Lord Monkey Fist. However, when Kim starts to grow suspicious about Yori’s sudden appearance in Middleton, she heads after them to get to get to the bottom of their predicament.

Ron comes home to unexpectedly find his new adopted baby sister named Hana Stoppable in his room. At the same time, he has to take care of a sack of flour for health class. Meanwhile, Kim and Ron team up with Yori to stop Monkey Fist yet again.

After discovering Hana walking on the ceiling, Kim and Ron try to get to the bottom of Hana's secrets. Meanwhile, Monkey Fist finds an ally in Yono the Destroyer as he continues his search for the "secret weapon".

High school graduation nears for the senior class, but Warmonga's return jeopardizes everything as Team Possible goes through their toughest odds yet to save the planet.

After both Kim and Drakken have been taken captive, Ron and Shego must race to rescue them from the clutches of Warmonga, Warhok, and the other invaders. All of the main characters must now band together to save the planet that they call home.