Background: Since the turn of the millennium, research within the field of substance-related problems has grown rapidly. This paper maps the effectiveness of existing research on substance use, misuse, abuse, and addiction prevention. Method: In this systematic mapping review, we searched the Web of Science, PubMed, and PsycINFO using multiple terms related to substance use, misuse, abuse, and addiction prevention to assess systematic reviews evaluating prevention interventions. All records were assessed by two independent reviewers. Information about population, substances targeted, and effectiveness were extracted for each of the included reviews. The evaluated interventions were categorized into 12 types of interventions. Result: For the 532 reviews mapped, we found 12 types of interventions dividedinto two major categories: individual-focused interventions (n = 451) and population-based interventions (n = 111). For each intervention category, many reviews showed positive effects for technology-based interventions, multimodal interventions, and drink-driving interventions. The mapping also highlights areas, including physical activity and interventions in specific arenas, where the reviews present very inconsistent results. Conclusions: The findings presented in this review serve as a guide of existing research that can be used to inform practitioners and policy makers about interventions conducted as well as highlighting important areas for future research.