Among the most profound results presented at the 2024 European Society for Medical Oncology (ESMO) Congress were the 10-year data from the Checkmate-067 and Keynote-006 trials of Opdivo and Keytruda as first-line agents in advanced or metastatic melanoma in which 10-year overall survival topped 40%. The success of checkpoint blockade, however, has not extended to all tumor types, but in 2024, molecular studies have led to advances in gene therapies and a multitude of approaches that have opened the door to hope.