The Arab region is characterized by arid and semi-arid conditions with very limited renewable water resources. Most of the surface water comes from transboundary streams and most of the groundwater resources are fossil in nature. Water quality degradation and excessive use of pesticides and herbicides in agriculture pose severe environmental and health risks. The underlying research is a joint effort between Cairo University and the Technical University of Berlin to develop technologies and strategies for sustainable pesticide-free agriculture using saline or brackish water. This project builds on a previously implemented project in Spain by the German research partner that introduced the concept of Watergy, which presents an integrated desalination horticulture solar greenhouse. In this current research, the Watergy greenhouse is further developed to meet more arid climate requirements, reduce construction costs, and increase resource utilization efficiency. Several lab-scale experiments and a 100 m2 prototype were built in Egypt to optimize the process and answer research questions. Lessons learned from this project provided guidelines on the development of the most efficient approach of desalination and water management in the system, devised a cost-effective and efficient heat exchanger using low-cost local material, and established the feasibility of the system in the arid climate together with prospects for wider applications. The proposed greenhouse was estimated to be able to save in irrigation water 40% for cherry tomatoes and cucumbers, and 50% for bell peppers. Maximum crop yield can be achieved at extended upper salinity levels using the proposed greenhouse as follows: from 1,000 to 1,700 mg/L for cherry tomatoes; from 960 to 2,000 mg/L for bell peppers; and from 1,600 to 2,700 mg/L for cucumbers.