System signatures have transitioned from an emerging topic to a growing research area. It has become essential to classify different research directions and examine the general trends of this promising research area. This would help in identifying potential research areas requiring future study. In this article, we review the literature on “system signatures,” dating back to 1985, and provide a thorough insight into this research field by using the techniques of bibliometric and network analyses. We proceed by identifying 539 published studies, and then scrutinize them to find works of proven influence, based on citation and PageRank analysis, and those authored by influential researchers. We also pinpoint the top contributing countries and key research topics. Finally, we identify and propose seven research clusters which might provide a robust roadmap for further investigation. © 2021 Taylor & Francis Group, LLC.