Introduction: Only a limited number of recent phase III studies with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), mTOR-inhibitors or immune checkpoint inhibitors (ICI) in metastatic clear-cell renal cell carcinoma (m-ccRCC) could show an overall survival (OS) benefit compared to standard of care. We aimed to study the evolution of OS of m-ccRCC patients during the last 20-years period (2000–2020).