In the Japan of the future, employing androids for various purposes is nothing out of the ordinary. However, treating androids on the same level as humans is frowned upon, and there is constant paranoia surrounding the possibility of robots defying humans, their masters. Those who appear too trustworthy of their androids are chided and labeled "dori-kei," or "android-holics." High school student Rikuo Sakisaka notices when his house droid, Sammy, starts behaving curiously—she has been leaving the house without his instruction. When he inspects the movement logs in her database, a cryptic line grabs his attention: "Are you enjoying the time of EVE?" Accompanied by his friend Masakazu Masaki, Rikuo tracks the whereabouts of his houseroid to a cafe called Time of Eve, where it is forbidden for customers to display prejudice against one another. The cafe, Rikuo realizes, is frequented by both man and machine, with no evidence to tell either apart. Each customer—from the cheerful Akiko, to a robot dangerously close to breaking down—has their own story and challenges to overcome. While Rikuo tries to reveal Sammy's intentions, he begins to question the legitimacy of the fear that drives humans to regard androids as nothing more than mere tools.

A video blogger attempts to fake cryptid sightings to boost his views, but gets more than he bargained for when his crew is slaughtered by a real monster. Elsewhere, students find themselves preyed upon by a sandworm-like beast, initiating a desperate struggle for survival on their own school grounds. With more of these attacks from mysterious creatures occurring, researcher Sousuke Banba tasks himself with delving into the mystery. With nothing but the keyword "Kagewani" to lead him, he scours the sites of recent attacks in hopes of finding a lead to eradicating the creatures for good. However, Sousuke finds that these threats to humanity are even closer to home when the pharmaceutical company, Sarugaku, starts to encroach on his investigation.

After surviving the onslaught at Sarugaku headquarters, Sousuke Banba resumes his investigation of the Kagewani monster hybrids. Armed with the ability to harness the Kagewani's power, the researcher now has a means to eliminate the creatures. But despite the benefits of this skill, it has one major drawback: Sousuke now struggles to maintain his sanity, with the power threatening to consume his body. Soon, threats old and new begin to rear their heads, as the upper echelons of Sarugaku become active once again and an assassin with a personal vendetta sets her sights on Sousuke. Nevertheless, he resolutely forges ahead on his mission, determined to track down the origins of the Kagewani and eliminate their threat once and for all.

Patema is a plucky young girl from an underground civilization boasting an incredible network of tunnels. Inspired by a friend that mysteriously went missing, she is often reprimanded due to her constant excursions of these tunnels due to her royal status. After she enters what is known as the "forbidden zone," she accidentally falls into a giant bottomless pit after being startled by a strange creature. Finding herself on the surface, a world literally turned upside down, she begins falling towards the sky only to be saved by Age, a discontented student of the totalitarian nation known as Aiga. The people of Aiga are taught to believe that "Inverts," like Patema, are sinners that will be "swallowed by the sky," but Age has resisted this propaganda and decides to protect his new friend. A chance meeting between two curious teenagers leads to an exploration of two unique worlds as they begin working together to unveil the secrets of their origins in Sakasama no Patema, a heart-warming film about overcoming differences in order to coexist.