Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer and accounts for approximately 25% of nonmelanoma skin cancers (NMSC). Although the majority of cutaneous SCC lesions have been treated successfully by surgical excision, cryotherapy, electrodessication, or Mohs micrographic surgery, some locally advanced SCC patients are either inoperable, have been metastasized, or both. In such patients, treatment is more challenging due to limited options. We reviewed the literature to describe the mechanism of anti-PD1 agents in cancer therapy and current PD-1 blockade immunotherapy trials in cutaneous SCC. Currently, cemiplimab is the only anti-PD1 agent approved by the Food and Drug Administration for the treatment of locally advanced or metastatic SCC. This review described other anti-PD1 agents, such as pembrolizumab and nivolumab, that have depicted promising effects in advanced SCC, resulting in reduction of tumor size with minimal adverse effects. Immunotherapy targeting the PD-1-PD-L1 axis must be considered for advanced cutaneous SCC patients that are refractory to first-line of procedural treatment options.