The series was created by Fresh TV, the same studio behind 6teen, Total Drama, and Stoked, and was based on a 2010 television film of the same name.

After the show was not picked up for a third season, the creators explored the possibility of a second movie, but it never came to fruition.

In 2015, executive producer and lead writer Tim Burns revealed via Facebook that the team tried hard to make a third season or a second movie happen, including having already created story ideas for the 'Lucifractor' storyline and several scenarios for a sequel film, but they ran into problems with broadcasters, budgets, and keeping the young cast together.

Filming for the 13-episode second season took place from September 21 to November 17, 2011, and Disney Channel renewed the show for that season on the very same day filming wrapped.

Actor Ari Cohen, who played the father Ross Morgan, had his name dropped from the opening credits in season two, with his character appearing only in a recurring capacity.

The character Jesse, a vampire cult leader, was a main character in the original film but did not initially appear in the series because he was assumed to be dead, only reappearing in the season finales of both seasons.

A companion browser game called 'Humans vs. Vampires in 3D' was developed by Secret Location for Teletoon, letting fans play as humans or vampires with points counted toward an overall site tally that affected the outcome of the season finale.

Due to the video game's fan-voting results, the season one finale on Teletoon aired with an extra scene not shown on Disney Channel, tying the broadcast to the game's outcome.

The 'Humans vs. Vampires' game won a Canadian Screen Award for Best Cross-Platform Project in Children's and Youth and was also nominated for a Digi Award and a Kidscreen Award.