Set a few years in the future, Fred Jones opens an academy for training the newest mystery solvers. The series follows a team of students titled Team Red as they deal with rivals and solve mysteries.
- Laurel Stone - an eager teenage girl who leads Team Red.
- Kurt Ross - a jock teenage boy who serves as the muscles of the team, developing a crush on Jessica.
- Jessica Gutierrez - a gothic teenage girl who, despite her looks, cares about her teammates, later falling in love with Kurt.
- Nick Moore - a geeky teenage boy who serves as the brains of Team Red, being in love with Stephanie.
- Lucy the Cat - a sarcastic and brave cat who serves as Team Red's mascot.
- Scooby-Doo - the mascot of Mystery, Inc. who is now in charge of the pet division of Mystery, Inc. Academy.
- Shaggy Rogers - Scooby's owner/best friend who helps him with the pet division of Mystery, Inc. Academy.
- Headmaster Fred Jones - the leader of Mystery, Inc. who is now the headmaster of Mystery, Inc. Academy.
- Daphne Blake - the fashionista of Mystery Inc. who teaches beauty and martial arts at Mystery, Inc. Academy.
- Velma Dinkley - the brains of Mystery, Inc. who teaches sleuthing at Mystery, Inc. Academy.
- Cthulhu - a powerful cosmic-level entity who is revealed to be directly responsible for the TBD.
- Team Alpha, consisting of:
- Janice Ridge - an egotistical teenage girl who leads Team Alpha and cares about mainly herself.
- Anthony Rhodes - TBD
- Stephanie Lancé - a shy teenage girl who, unlike her teammates, cares about the other teams, having a crush on Nick.
- Michael Davidson - a rude teenage boy who TBD.
- Bites the Tiger - a vicious tiger who is rather TBD.
- Velma Dinkley/The Lamia - one of the teachers at Mystery, Inc. Academy who disguises herself as a lamia mainly to prove the new recruits' reflexes and skills.
- Benedict Ravencroft/The Neon Demon - a failing novelist who dresses as a glowing demon to get revenge TBD.
- Helena Knox/The Succubus - a bullied high schooler who disguises herself as a seductive TBD.
- Ivan Ora/The Mummy - a sarcastic ravager who TBD.
- Samantha Lewis/Hera - a rude and stuck-up scientist who disguises herself as the goddess Hera to show the world that she TBD.
- Gregory Thom/Dark Mutant - a lumberjack who uses toxic waste to remove trees easily, but has been arrested once. So he disguises himself as a dark mutant man to take down those who arrested him.
- TBD/The Vampire Queen - a [job] who is a TBD.
- The Black Knights - a group of criminals who are copying the original Black Knight and strike across the world.
- Some characters are designed after celebrities.
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