Purpose <p>Mental health literacy (MHL) is increasingly recognized as a core competency for future health professionals. In pre-licensure health professions education, MHL encompasses competencies relevant to both patient care and students’ mental health and well-being. Although a wide range of educational interventions have been implemented to improve MHL among health professions students, evidence on their outcomes, underlying mechanisms, and contextual influences remains fragmented and heterogeneous. This review aimed to evaluate the outcomes of MHL interventions in pre-licensure health professions education and to identify the mechanisms and contextual conditions that influence their impact.</p> Methods <p>A mixed-methods systematic review was conducted in accordance with the Joanna Briggs Institute methodology and PRISMA 2020 guidelines (PROSPERO CRD420251050891). Quantitative studies assessing changes in knowledge, attitudes, skills, confidence/self-efficacy, or behavioral and well-being outcomes were synthesized using a random-effects meta-analysis. Qualitative and mixed-methods studies exploring learner experiences and implementation factors were synthesized thematically. Findings were integrated using a convergent-segregated approach to provide explanatory insight into the observed quantitative effects.</p> Results <p>Fifty-five studies were included. The meta-analysis demonstrated a statistically significant, moderate improvement in knowledge following MHL interventions (standardized mean difference = 0.56). In contrast, pooled effects for attitudes, skills, confidence/self-efficacy, and mental health or well-being outcomes were not statistically significant and showed substantial heterogeneity. Qualitative synthesis identified three interrelated mechanisms associated with deeper learning outcomes: experiential contact, structured reflective practice with guided debriefing, and person-centered, recovery-oriented framing. These mechanisms were implemented inconsistently across interventions, helping to explain variability and the attenuation of pooled effects. Short-term or single-session interventions were sufficient to improve knowledge but provided less consistent evidence of benefit for attitudinal, skill-based, and behavioral outcomes, which appeared to be better addressed by longitudinal, experiential, and contextually embedded approaches.</p> Conclusions <p>MHL interventions in pre-licensure health professions education demonstrate consistent benefits for knowledge acquisition, while more complex outcomes depend on how interventions are implemented and embedded within curricula. Integrating cognitive learning with experiential and reflective pedagogies and delivering training longitudinally may be important for achieving meaningful and sustained outcomes. Mixed-methods integration provides insight into how MHL training may influence outcomes and the conditions under which it is most likely to be effective, informing the design of more robust and sustainable educational strategies for the future healthcare workforce.</p>