The story of Trauma Center New Blood follows a young doctor named Ryoji Muto, who is struggling to cope with the trauma he experienced during his time as an intern. After being attacked by his colleague, Dr. Harumi, Ryoji finds himself hospitalized and forced to undergo a radical treatment that involves using his newfound "trauma skills" to perform surgery on patients.
Gameplay in Trauma Center New Blood is fast-paced and action-packed, with players controlling Ryoji as he navigates through the hospital's corridors, completing surgeries and battling against monstrous creatures known as "Infection". The game features a unique combination of hacking mini-games and surgical simulations, requiring players to use their timing and reflexes to succeed.