In this chapter, we will explore the intricate relationship between our environment, diet, and genome. Genes influence our response to diet, while nutrients, or their absence, can impact gene expression. Over 90% of our genes have remained unchanged since the Stone Age when food availability was crucial for survival. We will examine the molecular basis for the recent adaptation of our genome to environmental changes, such as reduced UV-B exposure after migrating north and dietary opportunities due to dairy farming, like lactose tolerance. Most trait-associated variants in our genome are located outside protein-coding regions, often as regulatory SNPs within TFBSs. Nutrigenomics integrates elements from molecular biology and NGS technologies to investigate the effects of food on the epigenome, genome, transcriptome, proteome, and metabolome. These methods can be applied for comprehensive individual assessments, such as in diet intervention studies. The resulting datasets provide a foundation for optimizing personalized nutrition, aimed at preserving health and preventing nutrition-related diseases. Notably, utilizing the metabolome to characterize individuals has emerged as a powerful tool in personalized nutrition.