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- Velma Dinkley
- Mystery Inc. dopplegängers (single appearance)(VR simulation)
- Shaggy Rogers
- Fred Jones
- Daphne Blake
- Dr. Laslow Ostwald (final appearance)
- Princess Penelope Powerheart (single appearance)(VR simulation)
- Benji (single appearance)(VR simulation)
- Tad (single appearance)(VR simulation)
- Mitch (single appearance)(VR simulation)
- Osomons (single appearance)(VR simulation)
- Damian (single appearance)(VR simulation)
- Travis (single appearance)(VR simulation)
- Security kid (single appearance)(VR simulation)
- Sherlock Holmes (no lines)(VR simulation)(cameo)
- Dr. John Watson (no lines)(VR simulation)(cameo)
- Train passenger (single appearance)(VR simulation)
- Zombie kids (single appearance)
- Gooey-Oh (VR simulation)
- The Mystery Machine (real and VR simulation)
- Los Angeles, California
|Tad & Mitch||They were jealous of Dr. Ostwald making better video games than them.|
|Benji||He'd do anything to impress Princess Powerheart.|
|Princess Powerheart (Linda)||She was fired by Professor Ostwald and reduced to dressing up at the conventions.|
|Dr. Laslow Ostwald||He was using Velma to test his virtual reality game. The Osomons weren't real, and neither were her friends.|
|"Holiday"||Written by Xander Smith and Jennifer Finch||OtherStarPeople|
- Velma (and the rest of the gang) met Dr. Ostwald in the season two episode High-Tech House of Horrors.
- E-Scream was originally scheduled to air on April 23, 2005, but was preempted for ¡Mucha Lucha!
- Technically, there was no monster or bad guy or mystery in this episode, as the whole thing was just a game.
- This episode was released five months before it had aired on the DVD What's New, Scooby-Doo?: Volume 8 - Zoinks! Camera! Action!
- This is the only time in standard continuity that the Mystery Machine can change into another vehicle with the press of a button. Coincidentally, the van transforming into different vehicles was one of the gimmicks in the next series to follow, Shaggy & Scooby-Doo Get a Clue! This ability to transform the van was previously used in the series Amazing Chan and the Clan Chan.
- There were four clues that helped Velma solve the case.
- Fred didn't want the gang to split up.
- Daphne wore a green shoe instead of another purple one and didn't care about them not matching.
- Shaggy and Scooby actively volunteered to be live bait.
- The big giveaway was that Shaggy said "Toinks" instead of "Zoinks."
- This episode was included in Cartoon Network's Scooby-Doo! Back to School Marathon (August 10-11, 2013).
- The episode's title may be a pun on the gaming conference called E3.
- The Osomons are a play on either anime Pokémon or Digimon, the former of which also aired on the now defunct Kids' WB.
- The real Daphne dresses in a similar outfit to Catwoman's.
- Gooey-Oh is a play on another Kids' WB anime Yu-Gi-Oh! The hair on top of the toy also partly resembles Yugi's/Atem's spiky hair.
Animation mistakes and/or technical glitches
- Daphne's green shoe turns purple when Tad and Mitch walk away with their Gooey-Oh creature, and when she is taken away by the Osomons.
Inconsistencies/continuity errors and/or goofs/oddities
- The opening scare scene shows the Osomons coming out before Velma started playing the game. Perhaps Dr. Ostwald was exercising a scene he later decided to delete.
- Dr. Ostwald's simulator apparently defies the laws of space, since Velma (not knowing he was still in it) manages to move a long distance.
- It is strange that Velma, having "left" Ostwald's game, did not notice that her friends were no longer with the costumes they wore at the beginning of the episode.
- What's New, Scooby-Doo?: Volume 8 - Zoinks! Camera! Action! DVD released by Warner Home Video on February 21, 2006.
- What's New, Scooby-Doo?: Complete 3rd Season DVD set released by Warner Home Video on January 8, 2008.
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