This research investigates the dynamics of contaminant exposure in European hake (Merluccius merluccius, L. 1758) from the Adriatic Sea (Central Mediterranean Sea) by examining the levels of total mercury (THg) and polycyclic aromatic hydrocarbons (PAHs) in the muscle fish tissues. The study explores the correlations between these pollutants and somatic indexes to identify the early warning signals of pollution and ecological effects. The levels of pollutants are influenced by season and sex. Lipids appear to have a minimal effect on the PAH levels, whereas they exhibit a positive correlation with mercury levels in the muscle. No significant relationships between the pollutants and condition indexes were observed, except for a positive correlation between THg and the gonadosomatic index, indicating a potential impact on the reproductive health of fish. In contrast, PAHs showed no meaningful correlation with condition indexes. Differences in contaminant accumulations and lipid levels between sexes reflect variations in metabolic activity, reproductive costs, and adaptive strategies to seasonal changes and energy demands. This study highlights the importance of long-term monitoring to improve pollution management, environmental conservation, and the protection of marine organisms’ health.