Coastal acidification, warming, and nutrient management actions all alter water quality conditions that marine species experience, with potential impacts to their physiological processes. Decreases in calcite saturation state (Ω_Ca) and food availability, combined with warming water temperatures, pose a threat to calcifying organisms; however, the magnitude of future changes in estuarine systems is challenging to predict and is not well known. This study aims to determine how and where oysters will be affected by future acidification, warming, and nutrient reductions, and the relative effects of these stressors. To address these goals, an oyster growth model for Eastern oysters (Crassostrea virginica) was embedded in a 3-D coupled hydrodynamic-biogeochemistry model implemented for two tributaries in the lower Chesapeake Bay. Model simulations were forced with projected future conditions (mid-21st century atmospheric CO₂ and atmospheric temperature under Representative Concentration Pathway (RCP) 8.5, as well as managed nutrient reductions) and compared with a realistic present-day reference run. Together, all three stressors are projected to reduce Ω_Ca and growth of oyster shell and tissue. Increased atmospheric CO₂ is projected to cause widespread reductions in Ω_Ca. The resulting reductions in oyster shell and tissue growth will be most severe along the tributary shoals. Future warming during peak oyster growing seasons is projected to have the strongest negative influence on tissue and shell growth, due to summer water temperatures reducing filtration rates, enhancing shell dissolution and oyster respiration rates, and increasing organic matter remineralization rates, thus reducing food availability. Nutrient reductions will exacerbate deficits in oyster food availability, contributing to further reductions in growth. Quantifying the effects of these stressors provides insight on the areas in the lower bay where oysters will be most vulnerable to mid 21st-century conditions.