Renal Cell Carcinomas (RCC) are a diverse group of histologically and genetically distinct renal neoplasms accounting for 2.4% of all cancers worldwide. While a majority of RCC cases are sporadic in nature, a proportion are due to genetic predisposition caused by syndromic and non-syndromic conditions. Inherited renal cell carcinoma is associated with alterations in genes such as VHL, MET, FH, and FLCN and identification of these genes has been critical to understanding the molecular biology of both inherited and sporadic RCC, informing both clinical management and treatment. Despite the large number of known genes which are linked to RCC predisposition, most individuals with features of RCC predisposition do not harbour variants in known inherited RCC genes, suggesting additional unknown causes of heritability have yet to be uncovered. This study has utilised a range of genomic sequencing methodologies, scaling from single gene to whole genome sequencing, on individuals with features of renal cell carcinoma predisposition in order to identify novel causes of heritability associated with RCC. Multiple genomic sequencing approaches in these individuals has uncovered a range of potential genetic features that could be associated with predisposition to RCC, including genes not previously known to be associated with RCC, discovery of new molecular mechanisms of genetic inheritance for known RCC predisposition syndromes, and provided innovative methods for the identification and characterisation of molecular alterations in specific inherited RCC subtypes.