Non-melanoma skin cancers (NMSCs), including basal cell carcinoma and cutaneous squamous cell carcinoma, are typically managed with Mohs micrographic surgery, but advanced cases may require alternative approaches due to inoperability or progression. The immunogenicity of NMSCs makes them strong candidates for immune checkpoint inhibitor therapy, with agents like cemiplimab and pembrolizumab demonstrating favorable efficacy and tolerability. Emerging strategies, including neoadjuvant and intralesional immunotherapy, are under investigation to enhance tumor response prior to or in place of surgery. Continued development of these immunotherapeutic approaches offers the potential to improve outcomes in patient care.