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One key to avoiding ecosystem dysfunction is to better understand the connections between important ecosystem components that can be represented by flows of macronutrients such as carbon and nitrogen and units of energy such as lipids. The present end-to-end study of the North Sea used combinations of chemical-oceanographic information, pigment and lipid fingerprinting and bulk and compound-specific stable isotope analysis of phospholipid-derived fatty acids (PLFA) to describe trophodynamics and energy fluxes within and between the pelagic and benthic food webs. It was shown that small-sized phytoplankton such as Cyano-, Prasino-, Crypto- and Prymnesiophyceae are underestimated drivers of North Sea primary production and macronutrient fluxes, whereas hydrographic features such as terrestrial run-off and thermal stratification influence composition and quality of particulate organic matter (POM) as food for higher trophic levels. Biogeochemical analysis also revealed that seasonal changes in isotopic composition of routine POM samples may compromise the analysis of food webs when POM is considered as being representative for primary producers, because POM is often a complex mixture of isotopic end members that are influenced by physiological responses and/or early diagenesis.