Shiki Toono awakens in a hospital to find the walls and people around him covered in black lines. Unable to recall his past memories, Shiki is told that he survived a fatal car accident, which left a fragment lodged into his chest. His attraction to the lines lead him to trace over an object, revealing his ability to destroy it. After realizing only he is able to see these lines, Shiki is given a pair of glasses to mask them, before starting a new life with his relatives.

Eight years later, the death of his father leads Shiki back to the Toono mansion, his childhood home. One day, leaving school due to anxiety, he passes by a mysterious woman. A sudden urge overtakes him, and once again, he uses his ability to trace the lines that cover her. Soon after, he wakes up in the mansion, questioning whether what had transpired was a dream or reality.

Shingetsutan Tsukihime tells a tale enveloped in adventure, romance, and mystery. As Shiki begins to unveil his past, what lingers in the unknown soon comes back to haunt him.