Dr. Neo Cortex is a new character in Super Smash Bros. Crossover and a major antagonist starting with Season 21 onward. Cortex first appears with the other villains when they mock the captured heroes. Later, Uka Uka begins attacking Cortex after the heroes escape their clutches, as they were supposed to make the prison inescapable. Cortex is seen again during the second arc where he and the other villains are being chewed out by Uka Uka for their constant failures.
- Cortex's appearance is based off his appearance in Crash Bandicoot: The Wrath of Cortex, as that is the appearance he is most recognized in.