Immune checkpoint therapy has revolutionized the management of advanced cutaneous squamous cell carcinoma (CSCC). It is critical to assess efficacy in the real-world setting, including the population generally deemed trial ineligible due to poor performance status and immunosuppression. Thus, we aimed to evaluate the clinical benefit of response to anti-PD-1 therapy in a retrospective advanced CSCC cohort. To do so, we performed a real-world study of patients with advanced CSCC treated with immunotherapy from 2016 – 2020 at Massachusetts General Hospital. We report an objective response rate of 34%, including 14% with complete response and a disease control rate of 70%. The median PFS was 1.2 years and the median OS was 3.3 years. Response was likely independent of underlying immunosuppressive conditions and type of anti-PD-1 therapy, but patients with a poor performance status at baseline were associated with poorer outcomes on univariable and multivariable analysis. We demonstrate that the response rates to anti-PD-1 therapy among real-world advanced CSCC patients are comparable to efficacy in pivotal trial reports and appear independent of immunosuppression status. However, clinical performance status at baseline is a likely predictor of response to treatment.