One of the largest restoration programs in the world, the Comprehensive Everglades Restoration Plan (CERP) aims to restore freshwater inputs to Everglades wetlands and the Florida Bay estuary. This study predicted how the Florida Bay ecosystem may respond to hydrological restoration from CERP within the context of contemporary projected impacts of sea-level rise (SLR) and increased future temperatures. A spatial-temporal dynamic model (Ecospace) was used to develop a spatiotemporal food web model incorporating environmental drivers of salinity, salinity variation, temperature, depth, distance to mangrove, and seagrass abundance and was used to predict responses of biomass, fisheries catch, and ecosystem resilience between current and future conditions. Changes in biomass between the current and future scenario suggest a suite of winners and losers, with many estuarine species increasing in both total biomass and spatial distribution. Notable biomass increases were predicted for important forage species, including bay anchovy (+32%), hardhead halfbeak (+19%), and pinfish (+31%), while decreases were predicted in mullet (-88%), clupeids (-55%), hardhead silverside (-15%), mojarras (-117%), and Portunid crabs (-16%). Increases in sportfish biomass included the angler-preferred spotted seatrout (+9%), red drum (+10%), and gray snapper (+8%), while decreases included sheepshead (-40%), Atlantic tarpon (-73%), and common snook (-507%). Ecosystem resilience and fisheries catch of angler-preferred species were predicted to improve in the future scenario in total, although a localized decline in resilience predicted for the Central Region may warrant further attention. Our results suggest the Florida Bay ecosystem is likely to achieve restoration benefits in spite of, and in some cases facilitated by, the projected future impacts from climate change due to the system's shallow depth and detrital dominance. The incorporation of climate impacts into long-term restoration planning using ecosystem modeling in similar systems facing unknown futures of SLR, warming seas, and shifting species distributions is recommended.