Nutritional systems biology may be defined as the ultimate goal of molecular nutrition research, where all relevant aspects of regulation of metabolism in health and disease states at all levels of its complexity are taken into account to describe the molecular physiology of nutritional processes. The complexity spans from intracellular to inter-organ dynamics, and involves iterations between mathematical modelling and analysis employing all profiling methods and other biological read-outs. On the basis of such dynamic models we should be enabled to better understand how the nutritional status and nutritional challenges affect human metabolism and health. Although the achievement of this proposition may currently sound unrealistic, many initiatives in theoretical biology and biomedical sciences work on parts of the solution. This review provides examples and some recommendations for the molecular nutrition research arena to move onto the systems level.