"Sengoku Night Blood" is set in a fictional world where humans and vampires coexist, divided into two factions: the Eves, who are human, and the Nobles, who are vampires. The story unfolds in the land of "Tenka," a realm inspired by Japan's Sengoku period, where powerful warlords and their clans vie for dominance. The central conflict revolves around the struggle for control over the "Sacred Blood," a powerful resource that grants immense power to those who possess it. The Sacred Blood is said to be the key to uniting the land and ending the chaos.

The protagonist, Yuzuki Tachibana, is an Eve who becomes entangled in the conflict after being transported to Tenka from the modern world. Yuzuki possesses a unique ability to produce Sacred Blood, making her a target for both Eves and Nobles. Her arrival disrupts the fragile balance between the factions, as various warlords seek to use her power to further their ambitions. Among these warlords are iconic figures from Japanese history, reimagined as vampires or humans, each leading their respective clans. Notable characters include Oda Nobunaga, Date Masamune, and Sanada Yukimura, who are portrayed with distinct personalities and motivations tied to their historical counterparts.

As Yuzuki navigates this dangerous world, she forms alliances with key figures from both factions. Her interactions with the warlords reveal the complexities of their relationships, as well as the moral ambiguities of their actions. The narrative explores themes of loyalty, power, and the consequences of ambition, as the characters grapple with their desires and the greater good. The story progresses through a series of battles, political intrigue, and personal conflicts, with Yuzuki's role as the catalyst for change becoming increasingly significant.

The series blends historical elements with supernatural fantasy, creating a unique setting where the lines between friend and foe are often blurred. The characters' struggles are driven by their individual goals, whether it is to protect their clan, achieve personal glory, or seek redemption. The overarching plot builds toward a climactic confrontation over the Sacred Blood, with the fate of Tenka hanging in the balance. Through its exploration of alliances, betrayals, and the pursuit of power, "Sengoku Night Blood" presents a tale of conflict and coexistence in a world where the past and present collide.