Rapid urbanisation and water resource depletion have compelled regions worldwide to consider reverse osmosis desalination as a solution for securing a sustainable water supply. However, the sustainability of reverse osmosis desalination plants, especially in the Gaza Strip, remains a critical concern. So, a comprehensive evaluation of the sustainability of these facilities is essential. This paper presents a framework for assessing the sustainability of reverse osmosis desalination plants in the Gaza Strip, aiming to promote informed decision-making and address the multifaceted challenges associated with water resource management in this area. As a case study, the generated framework was applied to the southern desalination plant in Gaza. The framework integrates technical, environmental, economic, social, and institutional setup categories utilising various multi-criteria decision analysis methods such as the analytical hierarchy process, weighted summation, and swing methods. The framework was built depending on a list of sustainability indicators that were carefully selected and attributed to each sustainability category. Then, a group of local specialists in the desalination field were involved to determine the relative weight of the sustainability categories and their indicators. Finally, multi-criteria analysis was applied to find the global sustainability index that reflects the desalination plant's sustainability status. The southern desalination plant was found to be partially sustainable, with a global sustainability index value of 65. Finally, this research promotes sustainable water management in regions like the Gaza Strip by guiding informed decisions on reverse osmosis desalination plants, emphasising the need for ongoing sustainability efforts. © 2024, International Centre for Sustainable Development of Energy, Water and Environment Systems SDEWES. All rights reserved.