Puget Sound (Washington, USA) is a large estuary, known for its profitable shellfish aquaculture industry. However, in the past decade, scientists have observed strong acidification, hypoxia, and temperature anomalies in Puget Sound. These co-occurring environmental stressors are a threat to marine ecosystems and shellfish aquaculture. Our research assesses how environmental variability in Puget Sound impacts two ecologically and economically important bivalves, the purple-hinge rock scallop (Crassodoma gigantea) and Mediterranean mussel (Mytilus galloprovincialis). Our study examines the effect of depth and seasonality on the physiology of these two important bivalves to gain insight into ideal grow-out conditions in an aquaculture setting, improving the yield and quality of this sustainable protein source. To do this, we used Hood Canal (located in Puget Sound) as a natural multiple-stressor laboratory, which allowed us to study acclimatization capacity of shellfish in their natural habitat and provide the aquaculture industry information about differences in growth rate, shell strength, and nutritional sources across depths and seasons. Bivalves were outplanted at two depths (5 and 30 m) and collected after 3.5 and 7.5 months. To maximize mussel and scallop growth potential in an aquaculture setting, our results suggest outplanting at 5 m depth, with more favorable oxygen and pH levels. Mussel shell integrity can be improved by placing out at 5 m, regardless of season, however, there were no notable differences in shell strength between depths in scallops. For both species, δ13C values were lowest at 5 m in the winter and δ15N was highest at 30 m regardless of season. Puget Sound's combination of naturally and anthropogenically acidified conditions is already proving to be a challenge for shellfish farmers. Our study provides crucial information to farmers to optimize aquaculture grow-out as we begin to navigate the impacts of climate change.