<p>Severe burn injuries present significant global healthcare challenges, with outcomes significantly influenced by factors such as socioeconomic status, mental health conditions, and substance use, which vary across regions and healthcare systems. This study investigates the etiologies, treatment outcomes, and the impact of psychiatric conditions and controlled substance use on burn injuries in patients admitted to the intensive care unit at Switzerland’s largest Burn Center. Data were retrospectively analyzed from 438 patients admitted to the University Hospital Zurich Burn Center ICU between 2016 and 2022. Variables assessed included baseline characteristics, burn etiologies, injury mechanisms, treatment modalities, complications, discharge outcomes, and mortality. Statistical analyses employed generalized linear models and logistic regression. Most burns occurred at home/leisure activities (43.4%), 21.2% at work. Pre-existing psychiatric conditions were present in 38.8% of patients, and 24.4% were under influence of controlled substances at the time of injury. These factors were associated with higher complication rates, increased surgeries, longer hospital stays, and lower survival rates. The overall in-hospital mortality rate was 15.8%, significantly linked to a history of controlled substance use. These findings highlight the significant impact of psychiatric conditions and use of controlled substances on burn injury outcomes, underscoring the importance of an interdisciplinary approach to treatment and management, particularly for patients with mental health and substance abuse histories.</p>