Approximately 3–5% of patients with cutaneous squamous cell carcinoma (CSCC) develop advanced disease, accounting for roughly 1% of all cancer deaths in Australia. Immunotherapy has demonstrated significant clinical benefit in advanced CSCC in several key phase II studies; however, there are limited data for patients treated outside of clinical trials. This is particularly relevant in advanced CSCC, which is most often seen in elderly patients with significant comorbidities. Thus, we aim to describe our experience with immunotherapy in a cohort of patients with advanced CSCC in Australia. We retrospectively reviewed all advanced CSCC patients treated with immunotherapy within the Illawarra and Shoalhaven Local Health District. Among the 51 patients treated with immunotherapy, there was an objective response rate (ORR) of 53% and disease control rate (DCR) of 67%. Our most significant predictor of response was sex, with male patients more likely to have better responses compared to fe