The narrative of Trauma Team follows six protagonists who operate in different sectors of the medical profession, and their united conflict with a virulent infection dubbed "Rosalia".

The story was influenced by the 2009 swine flu pandemic, and reduced the usage of supernatural and science fiction elements prominent in earlier entries to create a more grounded narrative.

Trauma Team is a video game that combines simulation gameplay with non-interactive visual novel storytelling using fully-voiced motion comic segments.

[6][8] Surgery and emergency medicine follow the gameplay pattern of earlier Trauma Center titles, with characters working under pressure to save patients.

[9] Endoscopy has players guiding the endoscope through a patient's internal organs and carry out operations on small injuries such as ulcers, located using a radar.

Players navigate using the Remote functions to mimic the endoscope's motion, while the Nunchuck is used to steer, move the camera, and select medical tools.

[6][8][9] Compared to the other professions, diagnosis and forensics play very differently, being based around dialogue-based investigation and deduction with gameplay elements similar to point-and-click games.

Between these sections, the player looks over the described victims and medical reports which include X-rays and CT scans to deduce what the patient is suffering from.

Gabriel Cunningham is a diagnostician whose troubled personal life gives him a pessimistic view of humanity, and during the game he is reluctantly partnered with the AI system RONI.

Hank Freebird is an idealistic former soldier who changed careers after growing sick of violence, becoming Resurgam's resident orthopaedic surgeon.

CR-S01 is called from prison to perform a risky heart operation, done using the authority of Cunningham to save a key politician, and due to its success CR-S01's deal is struck.

Alongside these events, Maria confronts both her difficulty working with others and visions of Rosalia, a girl from her childhood; Tomoe successfully defies the restrictive heritage of her clan and saves her father from a life-threatening condition; Hank juggles his dual life as doctor and masked vigilante, in addition to helping a woman who attempted suicide to rediscover her love of life; and Cunningham struggles with the difficulties of his work and clashes with RONI, ultimately diagnosing his son's emerging Wermer's syndrome.

Ultimately there is a mass outbreak of the disease causing the black bruises, eventually diagnosed as a virulent strain of viral hemorrhagic fever.

With his memory returning, CR-S01 escapes captivity and goes with Maria to uncover more information, coming across a photograph of his adopted sister Rosalia Rossellini, later revealed to be the virus's natural host.

Her blood seeped into the surrounding Asclepias, with the monarch butterflies feeding on them becoming the virus's vector due to shedding their scales during their yearly migration.

[7] Supernatural and science fiction elements present in earlier titles, such as the Healing Touch, were removed or downplayed to promote greater realism.

Forensic medicine, inspired by the team's liking of crime dramas, focused on investigation over autopsies at the suggestion of Atlus USA.

[7] Due to a greater focus on action, programmer Takaaki Ikeda used programming modified from the script engine of Shin Megami Tensei: Nocturne.

A concept Kanada had to abandon was the lead doctor being openly gay; while appearing masculine, he would have a more feminine personality like a "strong elder sister", an archetype common in Japanese entertainment in addition to anime and manga.

While Japan had little problem with such characters, both his own research and consultation with Atlus USA made Kanada feel North American gamers might be offended.

Maria went through multiple redrafts, until Doi settled on making her an energetic archetype to balance against the calm Kimishima and innocent Tomoe.

Describing the art design, Doi called it a conscious move away from the color schemes of contemporaneous games, which seemed to favour a greyed or washed-out palette.

[22] Kanada requested a storytelling style unseen in the series, so Maeda designed the cutscenes as motion comics, with the camera panning over static and moving 2D images to create a 3D illusion.

[27] The vocal theme "Gonna Be Here" was composed by Kitajoh, with lyrics by Kobayashi and Atlus sound staff member Benjamin Franklin.

[22] The game's marketing created troubles inherent to the Trauma Center series as a whole with portraying its gameplay, and presented new challenges due to the wider range of medical professions represented.

[45] The pilot was shot in Los Angeles in early 2010 and starred Brandon Quinn, Eden Riegel, Jackson Davis and Julie Mond as a group of medical students who perform illegal surgeries for patients unable to afford proper treatment.

[46] Upon its debut week in Japan, Trauma Team failed to reach the top ten best-selling titles, coming in at nineteenth place.

[50] Chris Watters of GameSpot summarised the game with an overall positive view: "Though the characters and the activities have their flaws, the whole comes together impressively, making Trauma Team a great bet no matter what your specialty is.

"[6] GamesRadar's Andrew Hayward noted a lack of tension and faulted the forensic and endoscopy gameplay, but overall found the game enjoyable and praised its narrative and graphics over previous entries.

[3] Ryan Clements, reviewing for IGN, most enjoyed the surgery and emergency sections, but felt that the overall gameplay experience was mixed due to uneven implementation and pacing.