HIF-2α inhibitor combinations are being explored as a treatment option for renal cell carcinoma (RCC). The LITESPARK trials are investigating the use of these combinations, with some results already available, although the outcome of the phase III LITESPARK-012 trial has been reported as disappointing. Research and clinical trials on HIF-2α inhibitors and other treatments for RCC are ongoing, with various studies and trials examining their mechanisms, efficacy, and future directions.