Immune checkpoint inhibitor (ICI) combinations, as well as ICIs combined with tyrosine kinase inhibitors, have considerable potential for renal cell carcinoma (RCC) treatment. Newer targeted medications, gut microbiome, nanomedicines, and cyclin-dependent kinase (CDK) inhibitors demonstrate significant potential in preventing side effects and resistance associated with RCC treatment. Most patients, including those demonstrating long-term treatment effects, eventually demonstrate cancer progression. Nevertheless, recent studies have further revealed RCC pathogenesis and many acquired drug resistance mechanisms, which together have led to the identification of promising therapeutic targets. In addition to having roles in metabolism, immunogenicity, and the immune response to tumors, CDK4 and CDK6 regulate the cell cycle. Targeting CDK4 and CDK6, either separately or in combination with already approved treatments, may improve therapeutic outcomes in patients with kidney cancer. Other novel drugs, including pegylated interleukin 10, colony-stimulating factor 1 receptor inhibitors, CD40 agonists, and C-X-C receptor 4 inhibitors affect the tumor microenvironment and cancer cell metabolism. Moreover, a triple ICI combination has been noted to be efficacious. In general, compared with sunitinib as a single-drug treatment, newer ICI combinations improve overall survival in patients with RCC. Future research on the prevention of adverse events and medication resistance related to newer therapies may aid in ensuring effective treatment outcomes among patients with RCC. This article aims to summarize innovative immunotherapy drug combinations for RCC treatment and the mechanisms of action, drug resistance, and treatment of adverse events associated with these combinations.