Some of his most notable works include Tomie, a series chronicling an immortal girl who drives her stricken admirers to madness; Uzumaki, a three-volume series about a town cursed by spirals; and Gyo, a two-volume story in which fish are controlled by a strain of sentient bacteria called "the death stench."

[7] In the house where he lived, the bathroom was at the end of an underground tunnel, where there were spider crickets; such experiences were later reflected in his works.

[6] Ito began to draw manga at the age of 4, taking inspiration from the works he read in magazines.

[12] Film director Guillermo del Toro cited on his official Twitter account that Ito was originally a collaborator for the video game Silent Hills, of which both Del Toro and game designer Hideo Kojima were the main directors.

[20] In addition to Kazuo Umezu, and Shigeru Mizuki, Ito has cited Hideshi Hino, Shinichi Koga, Yasutaka Tsutsui, Edogawa Ranpo and H. P. Lovecraft as being major influences on his work.

[24] Ito has been inspired by horror since childhood, with his first manga being written about a protagonist with an eye in the middle of his hand, attacking him; this was heavily influenced by Shigeru Mizuki's Kappa no Sanpei.

[25][6] He has also found inspiration from Rakugo storytellers who tell Kaiden ghost stories, incorporating it into No Longer Human.

[6] He is also cited stating the schooling gave him more inspiration for his tools in drawing, namely pens and how to whittle pencils like dentures.

Much of his work is based solely in them, with other themes including a relationship of predator to prey, a loss of humanity, apocalyptic scenarios, and obsession being common.

[29][28][15] The universe Ito depicts is cruel and capricious; his characters often find themselves victims of malevolent unnatural circumstances for no discernible reason or punished out of proportion for minor infractions against an unknown and incomprehensible natural order.