Background: Keratinocyte carcinomas (KCs), including basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are the most prevalent malignancies globally, particularly affecting sun-exposed facial areas. Achieving clear surgical margins in these regions is essential to ensure oncologic control while preserving cosmetic outcomes. Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that enables real-time, high-resolution visualization of skin structures and may aid in margin assessment during KC surgery. This systematic review aims to evaluate the role of in vivo RCM in the surgical treatment of KCs. Methods: This review followed PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, Medline, and EBSCO databases was conducted for studies published between January 1992 and December 2024. Inclusion criteria focused on clinical studies utilizing in vivo RCM for diagnostic or surgical applications in KC management. Results: Eighteen studies involving 1112 patients were included. RCM was used preoperatively in 5 studies and intraoperatively in another 5. Nine studies assessed margin delineation, while eight focused on diagnostic accuracy. RCM improved diagnostic confidence and allowed for more precise margin assessment, potentially reducing the extent of surgical excision in cosmetically sensitive areas. However, its broader clinical adoption is limited by operator dependency, procedural complexity, and lack of standardization. Conclusions: RCM shows promise as a supportive tool in KC surgery, particularly for preoperative planning. While its diagnostic utility is well established, its intraoperative role requires further validation. Larger, standardized, and cost-effective studies are needed to confirm its impact on surgical outcomes and patient quality of life.