Mercury (Hg) settlements in the Mediterranean Sea determine a potential toxicological relevance of seafood intakes for coastal populations. To assess this possibility, fish, molluscs, and crustaceans of commercial size of 69 different species were sampled and analyzed for total mercury (HgTOT) from georeferenced areas and evaluated for their compliance with the European Union Maximum Residue Limits of 0.5 and 1.0 mg/kg wet weight (ww). Accounting for the weekly estimated seafood intake in the Italian coastal population (mean 469–626 g/person/week) it was then possible to recover threshold contamination values in seafood. Under a Tolerable Weekly Intake of 1.3 μg/kg/bw/week, a threshold seafood contamination <0.10 mg/kg ww has been derived for sensitive groups. A suitable algorithm based on the parallel MeHg and HgTOT analysis on the most consumed species, helped to refine the uncertainties related to the conservative assumption in seafood all the HgTOT present is in form of MeHg. This work aims to improve the link between the risk management and risk assessment strategies, with the identification of those fish and seafood species, that, when regularly consumed, could determine or prevent potential HgTOT/MeHg overintakes in sensitive groups.