Sorafenib is the first molecularly targeted drug for first-line treatment of patients with advanced kidney cancer and has achieved satisfactory results. Since then, a variety of molecularly targeted drugs have emerged, and the treatment of patients with advanced kidney cancer has entered a new era of molecular targeting. Molecular targeted therapy improves the clinical efficacy and response rate of patients, and prolongs the progression-free survival and overall survival of patients. Current targeted drugs include vascular endothelial growth factor inhibitors, mammalian target of rapamycin, immunological checkpoint inhibitors, etc. Understanding the mechanism of action and clinical efficacy of different targeted drugs, and analyzing the challenges of current targeted drugs from the perspective of gene mutation and drug resistance are helpful to the personalized treatment of patients with advanced renal cancer.