This article presents a case of renal cell carcinoma with inferior vena cava tumor thrombus and iliac vessel thrombosis (RCC-TT). The patient was admitted to the Urology Department of Jieyang People's Hospital in Guangdong Province. PET-CT and enhanced CT indicated a huge tumor in the right kidney, along with the formation of tumor thrombus in the inferior vena cava and right renal vein. Pathological examination of the right renal tumor biopsy suggested clear cell renal cell carcinoma. Through a multidisciplinary consultation on difficult cases in Guangdong Urological Association, we formulated a treatment plan combining targeted therapy with immunotherapy and regularly assessed its efficacy. The patient has completed seven courses of axitinib combined with tislelizumab and seven courses of lenvatinib mesylate combined with toripalimab treatment, with close follow-up during this period. Although mild adverse reactions such as skin itchiness and hematuria occurred, the follow-up CT imaging showed that the inferior vena cava tumor thrombus had decreased compared to before, and the iliac vessel tumor thrombus had disappeared. The subsequent surgical intervention will be performed after risk assessment at major domestic medical center. Currently, due to the lack of high-quality clinical research evidence, there is still controversy regarding the systemic treatment of renal cancer with tumor thrombus. This case affirms the positive role of targeted therapy combined with immunotherapy in reducing tumor thrombus and improving the quality of life in renal cell carcinoma with inferior vena cava tumor thrombus, which effectiveness, feasibility and safety are worth further research and exploration.