Hereditary cancer syndromes (HCS) account for 5-15% of cancers. They are associated with inherited germline pathogenic mutations of a group of genes called cancer predisposition genes most often comprising tumor suppressor genes following a loss-of-function model, and more rarely genes from heterogeneous canonical and non-canonical pathways such as oncogenic signalling. The pathophysiology of HCS varies according to the genes involved and the molecular mechanisms underlying malignant transformation. With advances in high-throughput sequencing technologies, a growing number of cancer susceptibility genes and a colossal number of germline variants have been recognised. With the progress of high-throughput sequencing technologies, a rising number of cancer susceptibility genes, as well as a colossal number of germline variants, are being recognized. Clinically, HCS are characterized by an increased risk of developing specific malignancies (cancer predisposition or susceptibility) at an earlier age than in the general population (often younger than 50 years) with a familial history of specific cancers belonging to the hereditary syndrome's tumour distinct spectrum, through generations. In the era of recent advances in precision medicine approaches, the molecular identification of germline variants allows specific surveillance programs for individuals at high risk for the early detection of cancers and the eventual targeted oncological therapies, as well as the prevention of subsequent cancers in patients and their at-risk family members. The recent validation of pathogenic germline variants as predictive biomarkers of prognostic predicting and drug response in an increasing number of cancer syndromes has led to the rapid adoption of more extensive germline genetic testing to guide their clinical management. Recently, the multigene panel testing that looks for mutations in several genes at once increases the likelihood of finding germline variants of unknown significance and eventual implications of distinct germline variants in multiple phenotypes. This book project will discuss the advances and impacts of predisposition genes in precision cancer medicine through common and uncommon familial cancer syndromes, the application of innovative techniques, including genomic, epigenomics and transcriptomic profiling tools and new therapeutic targets, as well as the new guidelines for clinical management of HCS.