Invader ZIM

Nickelodeon contacted Vasquez about pitching ideas for an animated series for their older demographic, and Invader Zim was the first thing he pitched. In Vasquez's words, "it went from pitch to series without hardly any waiting". As the series went on, ratings declined and budgetary issues became more frequent. Before the second season was completed, Nickelodeon canceled the series, leaving several episodes unfinished. The series originally aired on Nickelodeon from 2001 to 2002, with six of the completed second-season episodes initially going unreleased. These episodes were first released on DVD in 2004 and later debuted on the Nicktoons Network in 2006.

Invader Zim received positive reviews from critics and audiences, with praise primarily directed at its humor, writing, animation, art style, and the way it pushed the boundaries of what was considered acceptable on children's television. In the years since its cancellation, Invader Zim has often been listed among Nickelodeon's best shows. The series won an Annie Award, an Emmy Award and a World Animation Celebration Award, as well as receiving nominations for seven additional Annie Awards and a pair of Golden Reel Awards. Invader Zim has spawned its own fan convention called InvaderCON and a plethora of official merchandise, including video games, toys, clothing and accessories, among many other products. Despite its early cancelation and short run, due to increasing popularity and above-average merchandise sales it has been widely regarded as a cult classic.

A monthly comic book series of the same name was released on July 8, 2015, as a continuation of the television series and published by Oni Press until August 4, 2021. A film based on the television and comic series, titled Invader Zim: Enter the Florpus, premiered on Netflix on August 16, 2019.