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Cancer is a genomic disease caused by variants in genes that impact on the regulation of cell division, cell growth and cell death. While the majority of cancers are caused by acquired genomic variation, a significant minority are influenced by inherited genetic variation which can increase the chance of a person developing cancer in their lifetime. Inherited genetic factors can be monogenic or polygenic and also interact with other cancer risk factors to create an individualised risk profile. Understanding personalised cancer risk can facilitate precision screening, prevention and early detection strategies. In this review, we give an overview of constitutional genetic susceptibility to cancer, how to assess and identify enhanced susceptibility and exemplars of how this influences precision management.