Vasquez cited The Plague Dogs and Flight of Dragons as two of the most personally influential animated films he saw in childhood, while at the same time in live action, he found himself most influenced by Ridley Scott's Alien.

In September 1996, Vasquez announced in his introductory text to the sixth issue of Johnny the Homicidal Maniac that the comic book had been successful enough for him to quit his day job and focus on his art.

In 1995, Slave Labor Graphics began publishing a series of Johnny comics after Vasquez submitted samples of his artwork to them.

The series follows Johnny as he searches for meaning in his life, a quest that frequently leads to the violent deaths of those around him as well as, briefly, his own.

A photograph of one of Vasquez's friends, Leah England, serves as the middle of a portrait collection on the cover for the second issue of Johnny the Homicidal Maniac.

The Mini-Comic was a spin-off of a filler comic designed to replace a vacant page usually reserved for advertising space in the Squee!

In 2009, Vasquez collaborated with other alternative artists in Marvel Comics' Strange Tales, issue 2 of 3, with a story about MODOK.

[8] At Nickelodeon, Vasquez created the animated television series Invader Zim, which aired on the network and then later on Nicktoons.

Vasquez also did character designs for the Disney XD show Randy Cunningham: 9th Grade Ninja, as well as wrote for an episode of the online series Bravest Warriors.

[10] However, on September 30, 2016, Vasquez announced on his official blog that Very Important House was ultimately not picked up for a full series.

[11] The Art of Invader Zim, which released in 2019 mentioned that Very Important House was passed due to executive leadership changes at Disney Branded Television.

I dragged them, much like Big Sister there, out for a quick photo session and we had a damn fine time in freezing winds posing like the little, demonic wee ones that they are.

Being my niece, the youngest had no problem finding that place in her heart that allowed her to simulate the howling face of a child being dragged down a nightmare alley by an unspeakable horror.

Throw in a tall, monstrous friend of mine to stand in for Big Sister and you have four people with chattering teeth and trying to steal my jacket.

After that, the line-art came pretty easily enough, save for an adjustment period of finding the balance between a more realistic style and not losing the strange cartoonishness.He also worked on a Teenage Mutant Ninja Turtles short called Don Vs Raph, where Donatello and Raphael compete to see who is better, but the two always end up tying.

Vasquez's characters are often highly geometric and thin with heavy black outlines, almost to the point of resembling stick figures.

The protagonists in his comics are typically mentally unstable characters who live in dysfunctional societies, and whose manias are able to speak through inanimate objects.

His art style is very edgy and eccentric, and smiley faces are found throughout his artwork, trying to evoke an ironic sense of happiness in a world of chaos and darkness.