Because of the Gulf coast’s significantly increasing coastal population and highly trafficked shipping ports, concern for contaminants within marine ecosystems—which consequently can threaten the economy and impact human health—is growing. One area of particular concern is Tampa Bay, a highly urbanized estuary located in the center of Florida’s Gulf coast. Red drum (Sciaenops ocellatus) and snook (Centropomus undecimalis) are two of the most popular inshore, recreational saltwater fish species in Tampa Bay, prized for their fighting ability and culinary value, and, as such, are logical study species for evaluating the significance of contaminants to animal and human health. Contaminant studies generally focus only on one contaminant class, but our high-throughput quantification methods allow us to examine synergistic effects of multiple pollutants, focusing on sources, transfers, and correlations of several waterway contaminants, including phosphorus-based flame retardants, pharmaceuticals, ultraviolet filters, organochlorine pesticides, fecal sterols, phthalates, polycyclic aromatic hydrocarbons (PAHs), oxidized PAHs, aliphatics, polychlorinated biphenyls, and per- and polyfluoroalkyl substances. Our studies have documented high levels of contaminants of emerging concern in Tampa Bay fishes and this presentation details additional contaminant concentrations in red drum and snook muscle tissue. We document potential seasonal and spatial patterns, potential for bioaccumulation and biomagnification, and relationships to human consumption.