Renal cell carcinoma (RCC) encompasses a diverse group of histological subtypes with distinct genetic and molecular characteristics. Recent advances in genomics have elucidated the genetic and epigenetic mechanisms that drive RCC progression. This chapter aims to delve into these pathways as well as RCC subtype-specific genetic alterations seen in clear cell RCC, papillary RCC, and chromophobe RCC. Molecular profiling has revolutionized RCC treatment strategies by enabling the development of targeted therapies and offering promising potential for noninvasive monitoring and personalized treatment regimens. RCC is a complex and heterogeneous disease and remains an active area of investigation to better understand its biology, pathology, and genomics.