Cardiovascular disease (CVD) and cancers are overall still identified as the two most prevalent non-communicable diseases globally. Their prevention and potential reversal (in particular CVD risk) was seen effective with the modification of dietary intake that was applied in several different populations. Although the findings from epidemiological studies provide support that adhering to dietary patterns such as the Mediterranean diet can reduce incidence and prevalence of CVD and some forms of cancer, the mechanistic aspects of disease modulation associated with both diseases can be seen in dietary management. Several studies have already explored the potential modes of action of certain nutrients in well controlled large clinical trials. However, the clinical trials designed to determine the effects of adhering to a particular diet are relatively hard to conduct and these studies are faced with several obstacles particularly in the populations that are identified with a high risk of CVD or different cancers. Therefore, it is important to understand potential underlying and shared mechanisms of action and to explore how healthy dietary patterns may modulate the occurrence, initiation, and progression of such diseases. The aim of this review is to summarise and conceptualize the current understanding relating to healthy dietary patterns, and briefly discuss the opportunities that epigenetic research may bring and how it may assist to further interpret epidemiological and clinical evidence.