Reiji Kirio, formerly a corporate slave, wakes up one day in another world. After discovering that he has gained superhuman pharmaceutical knowledge, he decides to open up a drugstore alongside the canine Noera and the ghostly Mina. There, he tends to the needs of all who visit the shop with potions and the like. Cheat Kusushi no Slow Life: Isekai ni Tsukurou Drugstore follows the slow but often hectic days of Reiji's drugstore.

After being hit by a truck in the year 2014, Akira Natsume awakes to find himself inside a machine following a 16-year-long coma. As he adjusts to the new interface, he is greeted by police officer Minami Uezono and her android partner Alma. The pair shows Akira that his brain is contained inside a device called an EX-ARM—a weapon of mass destruction. Aboard an enemy smuggler ship, the three must escape using nothing but their ingenuity and combat skills. While initially reluctant to fight, Akira soon recalls his brother's words from before the accident. The memory inspires him to take action, possessing Alma's body to fight his opponents using martial arts. Once Alma plugs him into one of the ship's ports, he discovers the devastating potential of his EX-ARM by effortlessly hacking and assuming control of the vessel. Upon safely arriving back on land, Akira meets the other members of the EX-ARM Countermeasure Prevention Team, a police division working to mitigate the effects of EX-ARMs. Witnessing the atrocities committed by those who seek the power of EX-ARMs, he resolves to join the team and put an end to the terror caused by these weapons.

In the distant past, Miguel, the God of Destruction, was sealed inside the knight who ruled over light and darkness, Sturmhurt. Alongside the knight was Gestöber, who accompanied him through countless battles. In the present day, destiny causes them to reincarnate as Kabuto Hanadori and Seri Koyuki, two classmates. Their reunion should be a joyous moment, if not for the fact that these fantasied heroes are just products of Kabuto's delusions. As the fictional "Gestöber," Seri finds himself in various embarrassing situations due to Kabuto's antics that sometimes grow out of his control. Moreover, his classmate Utsugi Tsukimiya joins the fray with his absurdly accurate mind-reading abilities, slowly destroying Seri's social life. Seri tries hard to stay away from them, refusing to acknowledge their shenanigans, however with Kabuto's chuunibyou and Utsugi's unpredictability, he is only bound to be swept by the craziness coming his way.