Dubbed by some as "Mad Max meets Bambi",[1] it takes place in a mostly rural post-apocalyptic setting where some creatures are human/animal hybrids.

Gus, a young boy with deer-like features, lives a quiet life deep in the woods with his father.

Though he loves his religious father, he yearns to escape as he learns there is no fire past the trees but simply more land.

It turns out a mysterious plague has been wiping out humanity, and the leader of the facility, Abbot, along with scientist Dr. Singh, believe the half-animal, half-human children hybrids have something to do with it.

Eventually, though, Louise reveals she is pregnant, and Jepperd relents when a militia led by Abbot offers protection.

It was all a trick, however, with Abbot and Singh experimenting on pregnant women and hybrid babies to try to find a cure for the plague.

They find a bible that Gus's father wrote, but no evidence of a mother in her grave; on the way back to the camp, Singh starts to believe the writings.

Although the story is initially set in Nebraska, the landscape is inspired by Lemire's past home of Essex County, Ontario.

[2] Sweet Tooth, as a post-apocalyptic parable, is rife with influences such as Tim Truman’s Scout: War Shaman and the Winterworld three issue mini-series.

[2] Because the nature of monthly comics is dependent on sales, initially not even Jeff Lemire knew how many issues Sweet Tooth would run.

[7] In August 2020, a sequel series subtitled The Return was announced, set 300 years later and following a cloned Gus, beginning publication in November 2020.

[10] On May 12, 2020, Netflix had given the production a series order for a first season consisting of eight episodes and starring Nonso Anozie as Tommy Jeppard, Christian Convery as Sweet Tooth/Gus, and narrated by James Brolin.