Virtual Reality-simulations offer new opportunities for alcohol prevention in adolescents. As an innovative medium, Virtual Reality can be attractive for the target group, and avatar-based pathways allow tailoring prevention in a gender-specific manner. However, tailoring may reproduce gender stereotypes and be exclusive. Therefore, this systematic review aims to summaries existing evidence regarding Virtual Reality-simulations for alcohol prevention targeting adolescents and to examine how gender is considered. A systematic search was conducted in seven databases. Two reviewers independently performed screening, data extraction, and quality assessment. Out of 224 search hits, four publications derived out of an Australian, a Danish, and a US-American project met the inclusion criteria. Research designs included qualitative (2), quantitative (1), and mixed-method approaches (1). Qualitative methods focused on development, evaluation, and participatory methods in the creation process, demonstrating adolescents’ involvement in Virtual Reality design. Adolescents appreciated the realism and the exposure to peer pressure and to negative alcohol consequences. Quantitative designs focused mainly on measuring alcohol-related outcomes (e.g., attitude and behavioral intentions towards binge drinking), and positive changes were found. In all studies, gender was assessed in the male-female dichotomy. Further gender-sensitive research is needed to develop and test the possibilities and pitfalls of tailoring Virtual Reality-simulations.