The gameplay and presentation of Trauma Center use two recurring features: surgery simulation carried out from a first-person view, and the narrative delivered using a visual novel style.

[8][25][c] Trauma Team includes surgery, but also shows five other specialties: emergency medicine where patients at the scene are given rapid treatments, endoscopy for small-scale internal treatment of the respiratory and the GI tracts, orthopedics which focuses on skeletal operations and reconstruction, diagnosis for determining medical conditions through a routine of speaking with the patient and examining medical scans, and forensic medicine where evidence from crime scenes and the victims are used to reach a conclusion to the case.

[18][33] The Trauma Center series is set in a near-future version of Earth where medical advances have led to the development of cures for previously major diseases such as AIDS and cancer.

[7] A key organisation in the series is Caduceus: a medical research body for studying intractable diseases which also has a semi-covert role in fighting bioterrorism.

[43][23] A recurring narrative theme in the Trauma Center series is the passion of doctors to save lives, as well as the impact of bioterrorism on society.

[21] In Trauma Team, the story focused on themes of the preciousness of life and fear of death, drawing direct inspiration from the 2009 swine flu pandemic.

[25] Beginning production in 2004, the team wanted to recreate the surgical simulation gameplay of PC titles for the DS, since its controls and hardware were more capable compared to others of the time.

[47] Many of the staff were veterans of Atlus's role-playing game Megami Tensei, making production challenging due to the team's inexperience.

[56][57] Under the Knife was directed by Kazuya Niinou, who was later lead designer on the original Etrian Odyssey for Atlus, and would later work on titles for Imageepoch and Square Enix.

[1][2] Trauma Team began development in 2007, beginning as being similar to previous entries in the series before expanding into its current form, covering multiple medical professions.

[59] Joshua Jankiewicz of Hardcore Gaming 101 compared the series to Ace Attorney, noting that they were both introduced in the United States around the same time on the DS, and both had dramatic, anime-style presentations of an otherwise ordinary career.

[60] Chris Hoffman of Nintendo Power called Under the Knife a "breakthrough title" that proved that saving lives could be "just as satisfying and challenging" as "defeating bad guys".