When standard-of-care checkpoint blockade fails in metastatic melanoma, how can oncologists and interventional radiologists join forces to turn around patient outcomes? In this episode of the BackTable Podcast, medical oncologist Dr. Jennifer McQuade and interventional radiologist Dr. Rahul Sheth join host Dr. Tyler Sandow to discuss the growing evidence for intratumoral oncolytics as a therapeutic strategy for frontline immunotherapy-refractory melanoma and the interdisciplinary work that is required for successful implementation in practice.---SYNPOSISThe physicians review how engineered viral vectors, particularly RP1, complement checkpoint blockade through direct tumor lysis and immune activation, and summarize the IGNYTE trial data supporting their use in patients with metastatic melanoma refractory to anti-PD-1 and anti-CTLA-4 agents. The discussion then shifts to practical administration, highlighting the central role of interventional radiology in delivering these therapies to visceral and deep-seated lesions under image guidance. The doctors go on to address the nuances of patient and lesion selection, injection technique, and response assessment, including the importance of recognizing pseudo-progression. They place particular emphasis on the need for multidisciplinary collaboration and stakeholder buy-in efforts on the part of IRs seeking to integrate intratumoral oncolytic injections into their scope of practice. The episode concludes with a forward-looking discussion on the potential for expansion of oncolytic platforms into other solid tumors, underscoring this field as a growing, IR-forward frontier in cancer treatment.---TIMESTAMPS---RESOURCESWong MK, et al. RP1 Combined With Nivolumab in Advance Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025;43(33):3589-3599.https://doi.org/10.1200/jco-25-01346IGNYTE-3 Trialhttps://clinicaltrials.gov/study/NCT06264180