"Arknights: Perish in Frost" is an anime adaptation set in the dystopian world of Terra, a land plagued by a catastrophic mineral known as Originium, which both powers advanced technology and causes a deadly infection called Oripathy. The story centers on Rhodes Island, a pharmaceutical organization dedicated to researching Oripathy and providing aid to the infected, while also engaging in covert operations against oppressive regimes and rival factions.

The narrative unfolds in a cold, war-torn region where Rhodes Island dispatches a team to investigate a mysterious outbreak of Oripathy. The team, led by the enigmatic Doctor, includes key operators such as Amiya, a young Cautus with immense emotional and tactical intelligence, and Kal'tsit, a seasoned medic and strategist with deep ties to the organization's history. As they delve into the frozen wasteland, they uncover a conspiracy involving Reunion, a militant group of infected individuals fighting against societal oppression, and a shadowy corporation exploiting Originium for profit.

The plot explores themes of survival, morality, and the cost of progress, as the characters grapple with the ethical dilemmas of their mission. The Doctor's leadership is tested as they navigate treacherous alliances, internal conflicts, and the harsh realities of a world where the infected are ostracized and hunted. The story also delves into the backstories of key characters, revealing their motivations and the personal stakes they hold in the fight against Oripathy and the forces perpetuating its spread.

As the team uncovers the truth behind the outbreak, they face escalating threats from both human and environmental sources, including hostile factions, mutated creatures, and the unforgiving cold. The series balances intense action sequences with moments of introspection, highlighting the resilience and camaraderie of the Rhodes Island operators as they strive to protect the infected and challenge the systemic injustices of their world.