The Four Cardinal Heroes are a group of ordinary men from modern-day Japan summoned to the kingdom of Melromarc to become its saviors. Melromarc is a country plagued by the Waves of Catastrophe that have repeatedly ravaged the land and brought disaster to its citizens for centuries. The four heroes are respectively bestowed a sword, spear, bow, and shield to vanquish these Waves. Naofumi Iwatani, an otaku, becomes cursed with the fate of being the "Shield Hero." Armed with only a measly shield, Naofumi is belittled and ridiculed by his fellow heroes and the kingdom's people due to his weak offensive capabilities and lackluster personality. When the heroes are provided with resources and comrades to train with, Naofumi sets out with the only person willing to train alongside him, Malty Melromarc. He is soon betrayed by her, however, and becomes falsely accused of taking advantage of her. Naofumi then becomes heavily discriminated against and hated by the people of Melromarc for something he didn't do. With a raging storm of hurt and mistrust in his heart, Naofumi begins his journey of strengthening himself and his reputation. Further along however, the difficulty of being on his own sets in, so Naofumi buys a demi-human slave on the verge of death named Raphtalia to accompany him on his travels. As the Waves approach the kingdom, Naofumi and Raphtalia must fight for the survival of the kingdom and protect the people of Melromarc from their ill-fated future.

Marion is a young schoolboy who prides himself on his adherence to a philosophy he calls "rationalism". Because of his disdain for emotional display, he ignores anything remotely akin to affection. But when he's entangled in a romantic affair with an older courtesan, his rationalism is revealed to be little more than a cover for his own emotional immaturity. Learning to love, Marion blossoms under his older lover's care but unfortunately, Marion has yet to learn the true price of the affair.

Reeling from her recent breakup, Momo Ayase, a popular high schooler, shows kindness to her socially awkward schoolmate, Ken Takakura, by standing up to his bullies. Ken misunderstands her intentions, believing he has made a new friend who shares his obsession with aliens and UFOs. However, Momo's own eccentric occult beliefs lie in the supernatural realm; she thinks aliens do not exist. A rivalry quickly brews as each becomes determined to prove the other wrong. Despite their initial clash over their opposing beliefs, Momo and Ken form an unexpected but intimate friendship, a bond forged in a series of supernatural battles and bizarre encounters with urban legends and paranormal entities. As both develop unique superhuman abilities, they learn to supplement each other's weaknesses, leading them to wonder if their newfound partnership may be about more than just survival.

Two years ago, the death of Naoto Watari's parents left him as the sole caretaker for his younger sister Suzushiro "Suzu" Watari and forced him to move in with their aunt. So devoted is he to Suzu that he refuses to join clubs or even hang out with anyone, earning him snide comments and the title of "siscon" at his new school. But as long as Suzu is safe and happy, Naoto doesn't care what everyone else says. However, his sneering classmates may turn out to be the least of his worries. The sudden transfer of a girl named Satsuki Tachibana brings back traumatic memories from his past—a past she had a hand in making so unpleasant. Nasty secrets, unknown to Naoto, begin to surface with her arrival, threatening his new life.