Limited data exist on the use of immune checkpoint inhibitors (ICI) for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTR). We report a case of a SOTR who developed metastatic disease following multiple surgeries, three cycles of adjuvant radiotherapy, and minimization of immunosuppression. He was subsequently treated with pembrolizumab and achieved a complete response. However, the patient developed ICI-induced allograft rejection requiring therapy discontinuation. The allograft was salvaged following IVIg and steroids. The patient developed recurrent disease which failed rechallenge with pembrolizumab but achieved a partial response following cemiplimab administration. This case illustrates the potential to treat metastatic CSCC in a SOTR with anti-programmed death-1 therapy and preserve graft function despite allograft rejection.