Water resources management is a non-trivial process requiring a holistic understanding of the factors driving the dynamics of human-water systems. Policy-induced or autonomous behavioral changes in human systems may affect water and land management, which may affect water systems and feedback to human systems, further impacting water and land management. Currently, hydro-economic models lack the ability to describe such dynamics either because they do not account for the multi-factor/multi-output nature of these systems, and/or are not designed to operate at a river basin scale. This paper presents a flexible and replicable methodological framework for integrating a microeconomic multi-factor/multi-output Positive Multi-Attribute Utility Programming (PMAUP) model with an eco-hydrologic model, the Soil and Water Assessment Tool (SWAT). The connection between the models occurs in a sequential modular approach through a common spatial unit, the “Hydrologic-Economic Representative Units” (HERUs), derived from the boundaries of decision-making entities and hydrologic responsive units. The resulting SWAT-PMAUP model aims to provide the means for exploring the dynamics between the behavior of socio-economic agents and their connection with the water system through water and land management. The integrated model is illustrated by simulating the impacts of irrigation restriction policies on the Río Mundo sub-basin in south-eastern Spain. The results suggest that agents’ adaptation strategies in response to the irrigation restrictions have broad economic impacts and subsequent consequences on surface and groundwater resources. We suggest that the integrated modeling framework can be a valuable tool to support decision-making in water resources management across a wide range of scales.