Mussel farming is a major sector of Italian aquaculture, primarily based on the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1819). For an ecological perspective, this species is used as a sentinel organism due to its filtration capacity and ability to bioaccumulate contaminants. Within the AMICA project, a multidisciplinary study was conducted at a mussel farm in the Gulf of Pozzuoli, a well-known area under anthropogenic pressure, to investigate mussel physiological stress and metal accumulation. Shell length was measured in mussels collected in June 2024, from three farming ropes (R1, R2, R3). Trace metals (Al, As, Cd, Co, Cr, Cu, Fe, Ni, Pb, U, V, Zn) were quantified by ICP-MS in intervalvar waters and dried soft tissues. These matrices showed distinct patterns: intervalvar waters reflected ambient metal levels, whereas tissues acted as biological accumulators. Zn was markedly enriched in intervalvar waters, consistent with tight regulation, while Fe and V were substantially higher in tissues, suggesting greater retention. To link chemical patterns to physiological status, gill tissues were analysed for redox homeostasis by measuring Reactive Oxygen Species (ROS), lipid hydroperoxides (HPs), protein carbonyls (CO), in vitro susceptibility to oxidation (ΔHPs), and Total Antioxidant Capacity (TAC). ROS levels did not differ significantly among groups, although R3 showed a slight increase accompanied by higher HPs and ΔHPs, indicating enhanced oxidative pressure. CO remained stable, while TAC increased in R2 and R3, suggesting activation of antioxidant defences. These responses align with the elevated accumulation of V, Fe and Zn in R3, pointing to metal-induced oxidative stress. Size-class analyses further showed that larger individuals accumulated higher metal concentrations, confirming size-dependent bioaccumulation. Overall, the mussel farm appears influenced by environmental conditions of the study area, and the integrated chemical–physiological evidence provides a valuable baseline for understanding contaminant dynamics and ensuring the quality and safety of M. galloprovincialis.