This online educational activity provides clinicians with an in-depth review of the latest findings in head and neck squamous cell carcinoma (HNSCC) from ESMO 2025, highlighting advances in both resectable locally advanced and recurrent/metastatic disease. Faculty experts first explore new data on perioperative and adjuvant immunotherapy in locally advanced disease then discuss novel targeted and immunotherapy-based approaches that are showing promise in recurrent/metastatic disease. Safety profiles, patient-reported outcomes, and multidisciplinary considerations are addressed to support thoughtful integration of these therapies into real-world practice. These insights reinforce evolving strategies designed to enhance outcomes for patients across the full HNSCC spectrum.