Plastic pollution, particularly macro-plastic, poses significant threats to marine ecosystems worldwide, with adverse effects on marine megafauna such as mammals, seabirds, and sea turtles. This study examines the areas of higher risk of megafauna encountering floating macro-plastics in the Mediterranean and Black Seas, semi-enclosed basins with high anthropogenic pressures and plastic densities. Using Lagrangean and food-web models, we identify areas of risk by evaluating the co-occurrence and potential entanglement of floating macro-plastic with megafauna distributions for three years (2016-2018). The results show that continental shelves and open waters of the Western Mediterranean and the North Aegean/Levantine Seas are the most potentially impacted areas for marine mammals. In the Black Sea, the probability of encounter between marine mammals and macro-plastic is higher in the eastern shelf and seabirds have higher probability of encounter in the northwestern shelf. Seabirds in the Mediterranean Sea are more at risk of encountering macro-plastic in coastal areas, particularly in the Adriatic Sea. The analysis quantifies biomass exposure to varying plastic densities and estimates species-specific entanglement vulnerability scores, revealing that seabirds exhibit the highest exposure, followed by sea turtles and marine mammals. This study provides information to help understanding of the potential damage posed by plastic pollution on megafauna, contributing to the identification of priority areas for conservation and assessing the scale of ecological impacts.