<p>The contribution of urban wastewater treatment plants to pollution by emerging contaminants is still underestimated, and the discharge zones in water receivers are not always subject to adequate monitoring activities. In this study, the combination of risk level ranking of hazardous pollutants (potentially toxic elements and organic compounds) and assessment of the changes in metabolic activity and taxonomic composition of sediment microbial communities was applied. The ranking approach identifies the most harmful toxic elements in the local environment of the upper sub-catchment of the Iskar River, Bulgaria. The effect on microbial communities was assessed by determining the share of viable cells and inhibiting metabolic activity (using the fluorescent staining method with digital image analysis), as well as by examining changes in the taxonomic composition of the sediment bacterial microbiome. The data showed that Hg and Cu were the most concerning elements for the surface water matrix; Cu, Cd, and Pb pose the greatest risk in sediments. The organic compounds did not pose a risk. The microbial communities in the wastewater discharge area were affected by pollutants and by the high nutrients and organic content of the effluent. The implemented strategy offers a promising approach for enhancing future site-specific monitoring aimed at pollution control in water bodies that receive wastewater effluents, while also supporting an understanding of the potential ecological risks posed by hazardous pollutants.</p>