Cardio-metabolic and Nutrition-related diseases (CMDs) represent an enormous burden for health care. They are characterized by very heterogeneous phenotypes progressing with time. It is virtually impossible to predict who will or will not develop cardiovascular comorbidities. There is a clear need to intervene earlier in the natural cycle of the disease, before irreversible tissue damages develop. Predictive tools still remain elusive and environmental factors (food, nutrition, physical activity and psychosocial factors) play major roles in the development of these interrelated pathologies. Poor nutritional environment and lifestyle also promote health deterioration resulting in CMD progression. In the last few years, the characterization of the gut microbiome (i.e. collective bacteria genome) and gut-derived molecules (i.e. metabolites, lipids, inflammatory molecules) has opened up new avenues for the generation of fundamental knowledge regarding putative shared pathways in CMD. The gut microbiome is likely to have an even greater impact than genetic factors given its close relationship with environmental factors. In metabolic disorders, the discoveries that low bacterial gene richness associates with cardiovascular risks stimulate encourage these developments. Due to the complexity of the gut microbiome, and its interactions with human (host) metabolism as well as with the immune system, it is only through integrative analyses where metabolic network models are used as scaffold for analysis that it will be possible to identify markers and shared pathways, which will contribute to improve patient stratification and develop new modes of patient care.