This online CME activity examines advances in managing resectable locally advanced head and neck squamous cell carcinoma (HNSCC), focusing on the integration of perioperative immune checkpoint inhibitors (ICIs) and multimodal approaches. Faculty review current standards of care and highlight unmet needs that have driven investigation into combining radiation and immunotherapy. Emerging clinical trial data are discussed, including the impact of perioperative ICIs on event-free survival and pathologic response, with attention to patient selection informed by risk stratification and biomarkers. The program also addresses practical considerations for multidisciplinary care, including immune-related adverse event management and strategies to support patient access to these evolving treatment paradigms.