<p>Our visual abstract highlights the primary question of our work, which was to evaluate the outcomes of patients who received talimogene laherparepvec (T-VEC), an oncolytic herpes virus, for advanced Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC). While T-VEC has been approved for use in melanoma, it is currently only being used in the off-label setting for nonmelanoma skin cancer (NMSC). In addition, many of our patients received T-VEC with concurrent immune therapy, which is a patient population that has not been thoroughly studied. Data were obtained through a retrospective chart review of patients with MCC or SCC who received T-VEC at our NCI-designated comprehensive cancer center. The cohort included ten patients with MCC and three with SCC; six patients received T-VEC alone and seven received T-VEC with concurrent immune therapy. Of note, all three patients who had SCC also received immune therapy. The overall response rate (ORR) of the cohort, defined as the percentage of complete and partial responses to therapy, was 53.8%, with six complete responses and one partial response. Of the six complete responses, four patients were disease-free at their date of last follow-up, which was an average of 25 months from completion of T-VEC treatment. Our work highlights the fact that durable response to T-VEC for patients with advanced NMSC is possible in the setting of a high rate of concurrent immune therapy administration. Further work should more rigorously explore the role that T-VEC may play in NMSC, with particular attention to its use with immune therapy (<a href="https://doi.org/10.1245/s10434-026-19182-3">https://doi.org/10.1245/s10434-026-19182-3</a>).</p>