Cancer and metabolic syndrome (MetS) are associated with genetic mutation and often seen as the results of altered metabolic signals. Several nutraceuticals have been found to be effective in treating these diseases in clinical practice through the modulation of biochemical and clinical endpoints associated with the pathogenesis of cancer and MetS. In line with the availability of multiple interventions that could counteract the metabolic changes, there is mounting evidence for nutraceuticals as potential complementary medicine for these diseases on the foundation of their multi-factorial nature. Although cancer and MetS are the major contributors to deaths globally, the therapeutic effects of nutraceuticals and the role of nutritional genetics and nutritional genomics in the treatment of these diseases have not yet been explored in-depth. In recent years, many studies revealed that certain compounds are able to halt the progression of cancer and MetS and subsequently improve individual health through the regulation of metabolic gene expression. In this review, we examine the relationship of nutraceutical, nutritional genetics, and nutritional genomics in the context of personalized medicine. The discrepancies in response to bioactive food components due to inter-individual variabilities in genetics, epigenetics, transcriptomics, proteomics, and metabolomics are also discussed.