Suspended sediment concentration is an important estuarine health indicator. Estuarine ecosystems rely on the maintenance of habitat conditions, which are changing due to direct human impact and climate change. This study aims to evaluate the impact of climate change relative to engineering measures on estuarine fine sediment dynamics and sediment budgets. We use the highly engineered San Francisco Bay-Delta system as a case study. We apply a process-based modeling approach (Delft3D-FM) to assess the changes in hydrodynamics and sediment dynamics resulting from climate change and engineering scenarios. The scenarios consider a direct human impact (shift in water pumping location), climate change (sea level rise and suspended sediment concentration decrease), and abrupt disasters (island flooding, possibly as the results of an earthquake). Levee failure has the largest impact on the hydrodynamics of the system. Reduction in sediment input from the watershed has the greatest impact on turbidity levels, which are key to primary production and define habitat conditions for endemic species. Sea level rise leads to more sediment suspension and a net sediment export if little room for accommodation is left in the system due to continuous engineering works. Mitigation measures like levee reinforcement are effective for addressing direct human impacts, but less effective for a persistent, widespread, and increasing threat like sea level rise. Progressive adaptive mitigation measures to the changes in sediment and flow dynamics resulting from sea level rise may be a more effective strategy. Our approach shows that a validated process-based model is a useful tool to address long-term (decades to centuries) changes in sediment dynamics in highly engineered estuarine systems. In addition, our modeling approach provides a useful basis for long-term, process-based studies addressing ecosystem dynamics and health.