Background. Mental health is declining in health care workers. Objectives. To provide a comprehensive assessment of intervention literature focused on the support and treatment of mental health within the health care workforce. Search Methods. We searched online databases (e.g., Medline, PsycINFO). Selection Criteria. We selected manuscripts published before March 2022 that evaluated the target population (e.g., nurses), mental health outcomes (e.g., burnout, depression), and intervention category (e.g., mindfulness). Data Collection and Analysis. Of 5158 publications screened, 118 interventions were included. We extracted relevant statistics and information. Main Results. Twenty (17%) earned study quality ratings indicating design, analysis, and implementation strengths. Randomized controlled trials were used by 52 studies (44%). Thirty-eight percent were conducted in the United States (n = 45). Ninety (76%) reported significant changes, and 46 (39%) reported measurable effect sizes. Multiple interventions significantly reduced stress (n = 29; 24%), anxiety (n = 20; 17%), emotional exhaustion or compassion fatigue (n = 16; 14%), burnout (n = 15; 13%), and depression (n = 15; 13%). Authors' Conclusions. Targeted, well-designed mental health interventions can improve outcomes among health care workers. Public Health Implications. Targeted health care‒focused interventions to address workers' mental health could improve outcomes within this important and vulnerable workforce. (Am J Public Health. 2024;114(S2):S213-S226. https://doi.org/10.2105/AJPH.2023.307556).