The objective of this research was to better understand the dynamics of surface-groundwater interactions in a large Mediterranean watershed (Evrotas River Basin) and to improve the seasonal forecasting of a potential hydrological drought under future climate change scenarios. This is achieved by integrating the quasi-distributed watershed Soil and Water Assessment Tool (SWAT) model with the three-dimensional groundwater flow Princeton Transport Code (PTC) model. The combined models are applied to the alluvial plain of Evrotas watershed in Greece by considering the interaction between the stream network and the aquifer to better spatially represent feedback fluxes within the surface and groundwater domains. Model simulation (2007-2011) was in good agreement with field observations demonstrating that this integrated modeling approach provides a more realistic representation of the water exchanges between surface and subsurface domains and constrains more the calibration with the use of both surface and subsurface observed data. Finally, the integrated SWAT-PTC model was used to study the impact of future climate change on surface and groundwater resources of the area under three different climate change scenarios. The results indicate that the study area is very sensitive to potential future climate changes. Upstream reaches display a loss of surface water to underlying groundwater systems whereas downstream the main river receives recharge from groundwater as the water table approached the surface topography. The low flow characterization for the current situation shows that a large part of the stream network will be too dry to accommodate the development of a viable aquatic ecological community throughout the years. In dry periods, the amount of water that is supplied to the aquifer is 40.9% less than the amount of water that is supplied under current climate conditions highlighting the need for new management strategies that must be implemented in order to avoid setbacks in the allocation of water resources in the future.