Eight years after the third film, the OSS has become the world's top spy agency, while the Spy Kids department has since become defunct. A retired spy Marissa (Jessica Alba) is thrown back into the action along with her stepchildren when a maniacal Timekeeper (Jeremy Piven) attempts to take over the world. In order to save the world, Rebecca (Rowan Blanchard) and Cecil (Mason Cook) must team up with their hated stepmother. Carmen and Juni have since also grown up and will provide gadgets to them.
A retired spy is called back into action, and to bond with her new step-children, she invites them along for the adventure to stop the evil Timekeeper from taking over the world.