Renal cell carcinoma (RCC) accounts for nearly 2% of cancers diagnosed worldwide. For metastatic RCC, targeted therapy is one of the most common treatment methods. It can include approaches that target vascular endothelial growth factor (VEGFR) or rely on immune checkpoint inhibitors or mTOR inhibitors. Adenosine A2A receptor (A2AR) is a type of widely distributed G-protein-coupled receptor (GPCR). Recently, an increasing number of studies suggest that the activation of A2AR can downregulate anti-tumor immune responses and prevent tumor growth. Currently, the data on A2AR antagonists in RCC treatment are still limited. Therefore, in this article, we further investigate the clinical trials investigating A2AR drugs in RCC. We also describe the epidemiology and current treatment of RCC, along with the physiological role of A2AR, and the types of A2AR drugs that are associated with tumor treatment.