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The coastal region of Southern Italy’s Caserta province, known as the Litorale Domitio (Domitia coast) has been subjected to increasing pressure from unsustainably fast economic and urban growth in the last century, that resulted in a induced serious land degradation. To obtain a comprehensive picture of the ecological status of the Domitia coastal zone (Campania, Southern Italy), a holistic methodology has been applied. Sedimentological, geochemical, and biological analyses of the surface sediments and water samples were performed along the submerged beach. The data were integrated using a geographical information system, together with information on past and present land use and human activities along the coast and in inland regions. Heavy metal concentrations in sediments plus As and Se (Cd, Co, Cr, Cu, Hg, Ni, Pb, V, Zn) and their enrichment factors, which are important for identifying polluted areas in countries like Italy (where environmental legislation has not yet established intervention limits), indicate excesses Cd, Cr, Pb, and V of probable anthropogenic origin. A microbiological contamination of marine waters has been detected by the Regional Environmental Protection Agency of Campania. The Bacteriological Quality Index map shows that bathing areas must be classified as “contaminated” and “highly contaminated”. High levels of chemical and biological contamination are particularly common in both bathing seawater and sediments along the coastal zone south of the Volturno River, where the existing wastewater treatment plant is not properly working, to date. Factory farming, which is widespread in the area, is likely to be an additional important source of contamination. In accordance with these conclusions, analyses of the benthic diatom community revealed dominance of eutrophic species.