A major difference between infectious and non-communicable diseases is that infectious diseases typically have unique necessary causes whereas noncommunicable diseases have multiple causes which by themselves are usually neither necessary nor sufficient. Epidemiology seems to have reached a limit in disentangling the role of single components in causal complexes, particularly at low doses. To overcome limitations the discipline can take advantage of technical developments including the science of the exposome. By referring to the interpretation of the exposome as put forward in the work of Wild and Rappaport, I show examples of how the science of multi-causality can build upon the developments of omic technologies. Finally, I broaden the picture by advocating a more holistic approach to causality that also encompasses social sciences and the concept of embodiment. To tackle NCDs effectively on one side we can invest in various omic approaches, to identify new external causes of non-communicable diseases (that we can use to develop preventive strategies), and the corresponding mechanistic pathways. On the other side, we need to focus on the social and societal determinants which are suggested to be the root causes of many non-communicable diseases.