Estuarine fish populations, situated at the interface of land and sea, are affected by both land-based and ocean-based anthropogenic activities. Multiple, interactive factors such as nutrient inputs, complex trophic interactions, and fishing pose unique challenges when it comes to the management of estuary fisheries. The objective of our study was to quantify the effects of nutrient inputs, fishing effort, and species interactions on estuary fisheries harvest. Specifically, we developed a food web model that incorporates multiple trophic levels: nutrients, phytoplankton, herbivorous fish (prey), piscivorous fish (predator), with fisheries targeting both fish groups. We parameterized this model using data from Kāneʻohe Bay, an estuary system on Oʻahu, Hawaiʻi. We tested various nutrient regimes in combination with different fishing efforts and predation types (either generalist or specialist). Predation type was a strong driver of both the reciprocal effects between prey fishing and predator harvest, and the degree to which nutrient inputs impacted predator biomass and harvest. Scenarios with generalist predation exhibited less sensitivity to harvest of the other species. Overall, we found that elevated nutrient inputs can increase fisheries harvest and sustain greater fishing effort, with herbivorous prey species responding more than predators.