Barbamarco Lagoon is a small lagoon adjoining the Northern Adriatic Sea and is the site of a commercially valuable clam (Tapes philippinarum) fishery. A three-dimensional (3D) coupled hydrodynamic–ecological model was applied to the lagoon with the objective of assessing impacts on clam food supply, commercial harvests and water quality of different clam rearing strategies, lagoon morphologies and flow regimes. Harvest and net growth to seeding ratios, total harvest value, clearance efficiencies and clam satiety were used to quantify the commercial success of different management strategies, while bottom dissolved oxygen concentrations were used as an indicator of ecosystem health. Increasing exchange with the Northern Adriatic Sea or increasing freshwater inputs into the lagoon improved clam food supply and increased both harvest production and ecosystem health in model simulations of the system. Results indicated that the high spatial and temporal variability of clam production and water quality responses must be considered for a holistic assessment of the outcomes of strategies in the context of ecological and production carrying capacity.