Marine organisms are increasingly exposed to a combination of environmental stressors. However, most studies focus on single factors, limiting our understanding of real-world ecological challenges. This study investigates the combined effects of metal pollution, parasites, pathogens, and environmental variables on the health of Perumytilus purpuratus, a mussel species inhabiting the coast of northern Chile. The upwelling system in this area, combined with low water turnover, creates a unique environment in which to study how multiple factors interact. Mussels were sampled from several sites affected by metal discharges. Analyses revealed that individuals from central and northern sites exhibited the highest levels of parasites, pathogens, and tissue lesions. These health impacts were strongly associated with elevated pH, salinity, cadmium and copper concentrations in the water. Findings emphasise the synergistic effects of chemical and abiotic factors, underscoring the importance of incorporating multiple factors interactions into monitoring programmes. Such an approach can enhance predictions of ecological responses, inform conservation efforts, and guide policies addressing global challenges like aquatic pollution. Our study provides critical insights into how combined factors threaten aquatic ecosystems, offering a framework for more comprehensive environmental assessment.