Chase Suno and his friends, Jinja and Bren, are on a search for Chase's father, Jeredy Suno. However, they soon become involved in something else upon reaching their father's lab and becoming involved with an organism known as Monsuno. Chase, choosing to side with his father's work, denies S.T.O.R.M. access to the Monsuno and escapes. They are now on the run from the military organization, S.T.O.R.M., while still looking for Chase's father. However, a mysterious organization also has his eyes set on Chase and the group's Monsuno.

The 5 adventure-seeking teenagers are once again in the battle of Monsunos, now, however, with Jeredy Suno officially back from being missing or kidnapped. But along with old foes, come new ones, with The Forge Resistance, a manufacturer bent on destroying the world with Wild Core Bombs, The S.T.O.R.M. Strike Squad, a team which could be considered the anti version of Team Core-Tech handpicked by Charlemagne, the Hand of Destiny, a team of century-old tribes who have hidden themselves from the world underground long ago, and Six, a teenager clone of Dr. Eklipse. Now on Team Core-Tech's tail, Chase and his friends are ready to take the heat. But as the battle becomes tougher, the team must face new problems and must come to connect to their Monsunos than ever before.

The series continues after the events of Monsuno: Combat Chaos, with the introduction of Core-Tech and S.T.O.R.M's merging, Eklipse and Forge Resistance with the newly-manufactured Dino Monsuno, and return of Hand of Destiny with their new non-shapeshifting alien Monsunos. The three survived members of the Hand have been reverted to children- Petros, Terz and Dasha now work with Digby Droog. There are also some returning characters from Season 1, like the Bookman and Grandma Future. With the help of their new Hyper Monsuno, Team Core-Tech may stand a chance against their adversaries.