OBJECTIVES: To systematically review the effectiveness and harms of interventions to promote resistance and resilience regarding mental health and occupational stress issues among emergency medical service (EMS) clinicians. METHODS: We registered the systematic review prospectively on PROSPERO (CRD42023465325). We searched Medline, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, journals, and websites for studies published from January 1, 2001, through June 30, 2024. We conducted duplicate screening of titles and abstracts followed by full texts of potentially relevant abstracts. We included studies of EMS clinicians in high-income countries that evaluated interventions targeting resistance or resilience regarding mental health or occupational stress issues. We assessed the risk of bias and evaluated strength of evidence (SoE) using standard methods. RESULTS: We included seven studies (one randomized controlled trial, one controlled trial with a waitlist control, four pre-post studies, and one prospective cohort [single group] study) that evaluated a total of 425 EMS clinicians. We deemed five of the seven studies to have high risk of bias, one moderate risk, and one low risk. No meta-analysis was feasible because of heterogeneity in the interventions evaluated across studies. Mindfulness-building interventions targeting resistance and resilience among EMS clinicians were associated with reduced burnout at up to 6 months of follow-up (low SoE). The evidence was insufficient regarding the impacts of interventions targeting both resistance and resilience on anxiety and depression. No conclusions are possible for resistance-only or resilience-only interventions. No studies reported on the effectiveness of any interventions in reducing hospitalizations, post-traumatic stress disorder, substance use, suicidality, or withdrawals from the workforce. No studies reported on unintended harms of interventions. CONCLUSIONS: Given the sparse evidence identified in this systematic review, evidence-based options to improve mental health outcomes for EMS clinicians are very limited. Future research is urgently needed to inform strategies to address the many mental health and occupational stress issues that face the EMS clinician workforce.