The estuarine habitat mosaic supports the reproduction, growth, and survival of resident and migratory fish species by providing a diverse portfolio of unique habitats with varying physical and biological features. Global climate change is expected to result in increasing temperatures, rising sea levels, and changes in riverine hydrology, which will have profound effects on the extent and composition of the estuarine habitat mosaic and its associated nursery quality for juvenile fish. We used a spatially explicit bioenergetics model to assess how different climate change scenarios might affect juvenile salmon growth rate potential relative to present day conditions in the Nisqually River Delta, WA, USA. The model indicated that prey-rich habitats such as emergent salt marshes and eelgrass meadows were most likely to facilitate growth, and that reductions in their areal extent and accessibility could have severe consequences for salmon. For instance, unmitigated sea-level rise halved the predicted extent of low- and high-elevation emergent salt marsh, leading to a 30% reduction in end-of-season weights. Increasing water temperatures compounded these effects during the late spring and summer such that the average daily growth rate of an individual fish decreased by an additional 5–50% when compared to the effects of sea-level rise alone. Lethal temperatures (> 24 °C) were infrequently observed, but they were more likely to occur during summer low tides in the mudflat and eelgrass habitats when accessibility to prey-rich marsh was minimal, thereby limiting foraging capacity and the availability of thermal refugia. Our findings indicate that, barring the enactment of targeted management strategies, rising tidal levels and increasing ocean temperatures may reduce the quality of the estuarine habitat mosaic for out-migrating salmon and other sensitive fish species.