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Hydro-economic models can serve as valuable tools to improve the understanding of system details, as well as to support decision-making and water resources management. However, hydro-economic models are not practically implemented as intended and are mainly used in academic settings due to their complexity and data requirements. This study presents a holistic hydro-economic framework for sustainable water resources management, in a simple and understandable way for policy-makers. It is examined under various management, climate and pricing scenarios. The proposed framework is based on: (a) the modeling of water balance and (b) the use of various hydro-economic outputs (e.g., irrigation water value, farmers' utility, efficiency indexes, direct costs, etc.). The proposed methodology can be applied to data-scarce areas, such as the Lake Karla watershed, Greece. Lake Karla watershed is a typical rural Mediterranean area. The results are encouraging on hydro-economic modeling with limited data, indicating that the establishment of a new management approach could be very beneficial in terms of water use efficiency. Hence, this research can provide an appropriate and suitable approach for facilitating water management in agricultural areas and for implementing the European Framework Directive 2000/60/EC.