The treatment landscape for renal cell carcinoma (RCC) has evolved significantly, moving from early immunotherapies to targeted therapies and immune checkpoint inhibitors. In the 1980s, cytokine-based immunotherapies such as interferon-alpha (IFN-α) and interleukin-2 (IL-2) were first introduced, with IL-2 offering durable responses in a small percentage of patients, though limited by severe toxicities. The discovery of Von Hippel-Lindau (VHL) gene mutations in the 1990s led to the development of targeted therapies aimed at the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) pathways. VEGF inhibitors, including sorafenib, sunitinib, and pazopanib, revolutionised treatment by improving survival rates. Mammalian target of rapamycin (mTOR) inhibitors, like temsirolimus and everolimus, further expanded options for poor-prognosis RCC patients. In the mid-2010s, immune checkpoint inhibitors (ICIs) transformed RCC treatment by targeting programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4). Nivolumab and pembrolizumab, alone or in combination with other agents like VEGF inhibitors, became standard first-line therapies.