Estuarine environments are highly productive ecosystems exhibiting high fish biodiversity and richness. Estuarine bays yield significant fisheries catches, making them the target of extractive activities by both artisanal and industrial fisheries. These areas, however, are highly vulnerable to chemical contamination, such as polycyclic aromatic hydrocarbons (PAH) associated with oil spills and other anthropogenic activities, which can jeopardize animal health and consumer welfare. In this context, this systematic review aimed to evaluate PAH levels detected in seafood from estuarine bays throughout the entire American continent and assess potential human health risks. The PICO methodology was applied, and 27 experimental papers were evaluated. The findings indicate that naphthalene and pyrene are routinely detected at high concentrations in several species, such as white mullet and catfish, and that biliary metabolites concentrations tend to be higher than tissue levels. Although the effects of PAH on animal health are well defined due to several decades of assessments, food safety evaluations are still not routine, evidencing a significant knowledge gap and the need for legislative measures based on toxicological data.