The series reimagines the title character Martin Mystery and his stepsister Diana Lombard (after Martin's mother's death, Martin's father married Diana's mom) as 17-year-olds attending Torrington Academy, a high school in Sherbrooke, Quebec.
They work for the covert organization "The Center", which secretly protects the people of Earth from extraterrestrial and supernatural threats. Like all secret organizations, such as WOOHP, they must keep their work secret, thus anyone who comes too close to their missions, i.e. seeing a monster, will have their memories of the event erased.
Not everyone who works for the organization is human. The short and green-skinned alien, Billy, is one of Martin's best friends. Java works as a lunch server of Diana and Martin's school and is a caveman from 200,000 years ago; he also aids Martin and Diana on their missions. As far as "The Center" is concerned, Martin's vast knowledge of the supernatural and his remarkable intuition compensate for his poor personal hygiene and huge ego.
Diana resents these qualities at times, as Martin often does not seem to understand the seriousness of his missions, but generally loves him like any real brother. In a small twist of irony, Diana and Martin are lovers in the original comics version, and not step-siblings.