Marine fish play a crucial role in human diets by providing essential animal protein, particularly where other sources of protein are lacking. However, industrial activities in coastal regions can introduce pollutants that negatively impact the natural environment including aquatic organisms. This study aimed to assess the risks associated with pollution in water, sediments, and fish species—Sparus aurata and Dicentrarchus labrax—affected by aquaculture, urban rivers, and ports. To achieve this, physicochemical parameters such as pH, oxygen dissolution, chemical oxygen demand (COD), total dissolved solids (TDS), alkalinity, ammonia, nitrite, and nitrate were measured in three locations: Shatby, El-Max, and Anfoushi in Alexandria, Egypt. The research combined these measurements with molecular and biochemical endpoints to evaluate the impact of pollution. The results indicated a significant pollution impact on hepatic antioxidants, apoptotic-related genes, and DNA damage. Bacterial growth density was at its highest at El-Max, followed by Anfoushi and Shatby. Liver enzyme levels of glutathione transferase (GST) and glutathione peroxidase (GPx) were elevated in fish from El-Max and Anfoushi compared to Shatby. Additionally, metal concentrations of Zn, Mn, Cu, and Cd were higher at the El-Max site. Overall, the study highlights that pollution can alter the oxidative state and gene expression in aquatic organisms. The findings underscore the urgent need for stringent regulations to protect aquatic environments and ensure that fish, as a source of animal protein, remain safe for human consumption.