High-fidelity simulation (HFS) stands out as a pivotal asset in nursing education, particularly for honing medication administration skills. This review, aligned with PRISMA guidelines, analyzed 148 studies spanning 2012 to 2023, with only seven meeting inclusion criteria. Despite methodological limitations in the selected studies, a consistent trend suggests that HFS significantly enhances knowledge, competence, and confidence in safe medication administration among undergraduate nursing students. Importantly, the selection of HFS or other approaches should be contingent upon specific goals and intended learning outcomes. Notably, intervention groups consistently outperformed control groups, underscoring HFS's efficacy in elevating students' capabilities. However, the overall quality of the included studies was moderate, highlighting the need for more robust methodologies in future research. This study underscores HFS as a valuable approach in nursing education, providing essential insights for effective teaching practices. It emphasizes the imperative to consider alternative approaches based on educational goals and learning outcomes while advocating for further research on cost-effectiveness, measurement tools, and optimal simulation session duration.