The visuals do things to your eyes that no other anime is even attempting, every frame moves like someone poured liquid color into the camera and let it find its own shape. The plot doesn't exist to make sense; it exists to watch two people hold hands and pull weapons out of their subconscious while the world burns in chromatic aberration around them. Hand Shakers knows exactly what it is: a sensory experience that will either rewire your brain or give you a migraine, and it refuses to apologize for either outcome.

In a near-future Osaka, pairs of people called Hand Shakers can join hands to call forth Nimrodes, weapons drawn from deep within their minds. Touching hands also carries each pair into Ziggurat, a separate dimension where time stands still. There, Hand Shakers fight rival pairs for the right to challenge God, who will grant the victors a wish. Tazuna Takatsuki, an Osaka high schooler who loves tinkering with machines, takes a repair job at a university lab and meets Koyori Akutagawa, a girl who has been bedridden for a long time. She reminds him of Musubu, his late sister. When he takes Koyori's hand, he awakens as a Hand Shaker, but her life now depends on that bond: if he ever lets go, she will die. Their only hope of saving her is to reach God, so the two must learn to combine their powers and defeat the other pairs in this action series.