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 is thrown back into the action along with her stepchildren when a maniacal Timekeeper attempts to take over the world. In order to save the world, Rebecca and Cecil must team up with their hated stepmother. Carmen and Juni have since also grown up and will provide gadgets to them.

Harry, Ron and Hermione continue their quest to vanquish the evil Voldemort once and for all. Just as things begin to look hopeless for the young wizards, Harry discovers a trio of magical objects that endow him with powers to rival Voldemort's formidable skills.

In 1979 Ohio, several youngsters are making a zombie movie with a Super-8 camera. In the midst of filming, the friends witness a horrifying train derailment and are lucky to escape with their lives. They soon discover that the catastrophe was no accident, as a series of unexplained events and disappearances soon follows. Deputy Jackson Lamb, the father of one of the kids, searches for the terrifying truth behind the crash.