Several river basins in the world are faced with growing water scarcity and water use conflicts attributed to increasing water demand and competition among users, climate change and variability, and environmental degradation. Addressing these challenges necessitates shifting from the traditional uncoordinated sectoral approach to more integrated and fully participatory approaches supported by credible information generated by reliable and robust technical tools. Combining engineering, economics and hydroclimatological science, hydro-economic tools are well suited to provide reliable and impartial technical information that can support multi stakeholder negotiation and decision making processes in a river basin. This research develops and applies a detailed hydro-economic model to support multi-objective water resources assessments. The model supports integrated assessments of physical and economic impacts of changes in water demand, climate conditions, water resources management objectives and policies, and other system constraints on a basin's water resources. The main contribution of this research is the systematic coupling of detailed water resources and economic assessment models that are capable of (a) representing complex physical system characteristics and constraints; (b) simulating system operation at diverse temporal and spatial scales; and (c) representing water-based economic production processes at a basin scale. The research integrates a wide range of potential climate change impacts into the hydro-economic modeling framework through consideration of multiple future climate change scenarios from 13 Global Circulation Models under the medium and high emission projection scenarios. Economic uncertainty is characterized through conjunctive use of Monte Carlo simulation and Geometric Brownian Motion techniques to generate multiple forecast traces of important economic parameters. The model is applied to the Apalachicola-Chattahoochee-Flint River basin in the southeast USA as a case study.