In Detective Barbie 2: The Vacation Mystery, Team Barbie Detective (comprised of Barbie, Ken, and wheelchair-bound computer whiz Kelly) decides that it's time for a little time off from their usual crime-solving lives. That doesn't last long, however, as the team finds a new mystery as soon as they arrive at their vacation destination: the inn at Lighthouse Cove. It seems that some antique jewels have been stolen from the historic hotel. Barbie and her friends volunteer to investigate the mystery and solve the crime.

Detective Barbie 2 is primarily an adventure game where Barbie explores the inn and surrounding areas, such as the greenhouse and the lighthouse. Further, the inn was constructed by an eccentric inventor who built all kinds of secret passages and other surprises into the location. Find and use items, leverage your high-tech gadgets, interview the people who work at the inn, and solve the mystery.

In addition to the adventure elements, there are a few minigames which involve more traditional vacationing activities, such as flying on hang gliders and cruising on the water in speedboats.