- Acting for Two: Frank Welker voiced both Fred and Scooby in this series.
- In Memoriam: The premiere episode "There's No Creature like Snow Creature" was dedicated to the memory of Bob Onorato, who was a character designer for Scooby-Doo! and the Reluctant Werewolf and Scooby-Doo in Arabian Nights.
- The Original Darrin: After quitting the role four years earlier and being replaced by Billy West for Scooby-Doo on Zombie Island and Scott Innes for the video games and direct-to-video films that were released in that time, Casey Kasem returned to the role of Shaggy from here until Scooby-Doo! and the Samurai Sword.
- The Other Darrin:
- After Don Messick's death, Frank Welker took over the voice role of Scooby-Doo, in addition to voicing Fred as he always did, which resulted in Scooby-Doo sounding more like Brain from Inspector Gadget.
- Velma was recast from BJ Ward to Mindy Cohn, which made her sound more like Mandy from Grim and Evil (ironically, Mandy was voiced by Grey DeLisle, who was Daphne's voice actress since 2001).
- Also, in "The Vampire Strikes Back", Kimberly Brooks did double-duty and voiced both Luna & Dusk of the Hex Girls (although the episode's credits claim that Dusk's usual actress, Jane Wiedlin from the Go-Go's, provided singing vocals).
- Technically speaking, this also applies to the flashback to Velma's fifth birthday shown in the episode "A Terrifying Round with a Menacing Metallic Clown", which depicted the gang as they appeared in A Pup Named Scooby-Doo. Rather than Carl Steven, who voiced young Fred in that series, the younger Fred is simply voiced by his usual voice actor Frank Welker using a higher-pitched version of Fred Jones' normal voice.
- Production Posse: Several voice cast members from The Fairly OddParents! can often be heard on this show; not only does Grey DeLisle (Vicky) voice Daphne (having previously voiced the character in Scooby-Doo and the Cyber Chase), there have been several times where Tara Strong (Timmy), Daran Norris (Cosmo), Susan Blakeslee (Wanda), Carlos Alazraqui (Mr. Crocker), Kevin Michael Richardson (various other characters), even Adam West in one episode.
- Role Reprisal: Besides Casey Kasem returning to voice Shaggy and Frank Welker voicing Fred as usual, Grey Delisle voices Daphne, a role she previously assumed in Scooby-Doo and the Cyber Chase.
- Technology Marches On: Also like The Fairly OddParents!, the show heavily emphasized the use of modern technology, such as characters having cell phones, Velma researching things on a laptop computer, the Mystery Machine being equipped with GPS and other modern tracking technology, and a number of Internet-related jokes. This was to make the show look more realistic and up to date, compared to the previous shows, when such technologies didn't exist at the time (although in A Pup Named Scooby-Doo, Daphne did have a cell phone, and Velma had a bulky computer stored into a suitcase for typing data on.)
- Unintentional Period Piece: This show nowadays definitely serves as a look at what the early-to-mid 2000s was generally like for teens and young adults and what was popular back then.
- Wag the Director: Nothing new for the franchise, but after Casey Kasem, a vegan, quit voicing Shaggy for five years when forced to voice him in a Burger King commercial, he agreed to return for this show on the condition that the Big Eater would be portrayed at least as a vegetarian.
Trivia / What's New, Scooby-Doo?