Work zones are crucial for infrastructure maintenance and improvement. However, ongoing projects within work zones sometimes can place workers and drivers in dangerous situations. Despite safety regulations, work zone accidents persist with notable severity and frequency. Previous research has explored work zone accident causation, but it has not provided a comprehensive understanding of the factors that impact work zone safety. This paper addresses this research gap by following a multistep methodology. First, a systematic literature review (SLR) was conducted to identify a comprehensive list of 37 factors impacting work zone safety. Second, social network analysis (SNA) was employed to analyze the connectivity between these identified factors, based on the theoretical, mathematical, and computational approaches found in the literature. Third, the factors were grouped into clusters using the k-means clustering technique, considering the overall discussions present in the literature. Last, association rules were mined from the clustered factors to determine combinations of factors that have not been extensively examined together, thereby identifying gaps and deficiencies in the present body of knowledge. The findings of the SNA indicate that design-related factors have received more extensive attention in the literature, whereas certain driver- and state-related factors have received comparatively less attention. The clustering analysis shows that a significant number of theoretically addressed safety factors in the literature frequently are examined together, which indicates a necessity for additional computational and mathematical investigations to gain a more comprehensive understanding of these factors. Moreover, the association rules highlight the groups of underexamined relationships of factors that affect work zone safety. Ultimately, this research contributes to the body of knowledge by consolidating the studies concerning work zone safety and using them to provide a robust roadmap for future research, thereby enhancing the advancement of this field and ultimately leading to improved work zone safety practices.