Book excerpt: Human populations that have recently undergone substantial changes in their traditional social, cultural, and dietary habits have shown an increased susceptibility to developing chronic diet-related diseases concerning their genetic background. One factor is that the population's adaptive genetic variants related to its evolutionary history are exposed to different physical and lifestyle environments that underlie and influence the current patterns of disease risk. Under this perspective, the current obesogenic environment has promoted the acculturation of a westernized diet disrupting the ancestral gene-foods/nutrients/bioactive compounds interactions, i.e., ancestral genetic/ethnic profile vs. modern lifestyle. Modern lifestyles, including unhealthy dietary patterns, have further impaired the consumption of staple foods with essential nutrients and functional properties, increasing the incidence of obesity and associated comorbidities. However, most conventional nutrition approaches targeting chronic diseases have limited impact on managing the leading non-communicable diseases affecting modern societies.