Background: Whey is the largest volume co-product of the dairy industry and over the last two centuries, a significant amount of research has been dedicated to uncover its chemical composition, and to better understand the biological activities of whey constituents. However, the detailed composition of the low-molecular weight components, especially the non-protein nitrogen, of whey is not fully elucidated and a systematic approach to identify and quantify this partially unknown fraction is required for the production of new value-added and high-quality products. Scope and approach: This review comprises up-to-date knowledge on the molecular composition of whey, and identifies the knowledge gap regarding the detailed profile of the low-molecular weight components in whey. The paper also provides advanced analytical techniques and methodologies applied in the foodomics research that have the potential to overcome existing challenges for the detailed molecular fingerprinting of whey and whey fractions. Key Findings and Conclusion: In order to improve utilization of all whey fractions and enhance the production of high-quality and safe whey-derived ingredients, the known-unknown part, “the dark matter”, of whey streams must be uncovered. Foodomics is an ideal approach for this task, allowing untargeted molecular screening of food products as a function of production processes. Untargeted screening of whey and whey streams is a key to gain deeper insights into the low-molecular weight components that end up in different whey streams during processing, including contaminants, and to understand the effect of different unit operations on the composition of whey in terms of minor components.