Objectives: To systematically summarize research employing serious games in nurse education, to examine their effectiveness, to provide recommendations and implementation strategies, and to suggest future directions for the development and application of serious games in nurse education. Design: A systematic review. Data sources: An online search of the CINAHL, Medline, PubMed, EMBASE, PsycINFO, SCOPUS, and Web of Science databases, and a manual search of the reference lists of selected studies or review articles published in English and Korean between 1990 and July 2020. Review methods. This systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Articles that employed a serious game approach in nurse education were included. Two authors independently screened and reviewed the articles and assessed the methodological quality using the Cochrane risk-of-bias tools. Results: A total of seven studies met the inclusion criteria: three randomized controlled trials and four quasi experimental studies. Heterogeneity was found across all studies regarding the application of serious games, platforms, and gamification elements. Most of the studies evaluated the effectiveness of serious games using knowledge tests, while two studies evaluated skills performance. Two randomized controlled trials and two one group before and after studies reported that the use of serious games improved nursing students' and nurses' knowledge and performance. Conclusions: This systematic review does not provide comprehensive insights into the effectiveness of serious games in nurse education. However, based on the evidence reviewed, we provide suggestions for developing and implementing serious games in nurse education to enhance students' knowledge and performance.