This paper reviews the results of three studies on the application of high-field proton Nuclear Magnetic Resonance (¹H NMR) spectroscopy and metabolomics to the assessment of different issues related to marine bivalves. The outcomes of such applications yielded insights into multiple aspects concerning the impact of cold storage on shellfish quality and the effect of natural and anthropogenic stressors on bivalve metabolic profiles. In the first work, the effect of different cold storage conditions on the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1819) was investigated, revealing substantial time-related changes both in the metabolic profiles and microbial loads of stored mussels. In the second study, the seasonal change and reproductive cycle were demonstrated to be the leading causes behind the fluctuation in the amino acid and carbohydrate contents in the European clam Ruditapes decussatus (Linnaeus, 1758). Finally, NMR metabolomics was applied for assessing the effect of lead and zinc short-term exposure on the metabolic profiles of two clam species, Ruditapes decussatus and Ruditapes philippinarum (Adams & Reeve, 1850). The results evidenced a sensible metabolic response upon metal pollution, pointing out a main variability in the content of amino acids and organic osmolytes in relation to both metal nature and bivalve species.