With the IMF disbanded, and Ethan (Tom Cruise) out in the cold, the team now faces off against a network of highly skilled special agents, the Syndicate. These highly trained operatives are hellbent on creating a new world order through an escalating series of terrorist attacks. Ethan gathers his team and joins forces with disavowed British agent Ilsa Faust (Rebecca Ferguson), who may or may not be a member of this rogue nation, as the group faces their most impossible mission yet.

Bill Murray, Dan Aykroyd and Harold Ramis take up their proton packs once more to battle the forces of evil in Manhattan! After waging a war on slime that cost New York City millions, the Ghostbusters find themselves out of business until an ancient tyrant, preparing a return to the Earthly domain through his portrait at the Manhattan Museum of Modern Art, sets his sights on Dana Barrett's baby as the new home for his wicked soul! With the help of the Museum's possessed curator, he plans to turn New York into a really scary place to live! Now only the Ghostbusters can save New York City, by turning paranormal pest control into an art form!