This paper adopts a holistic approach to the integrated water supply chain system, considering water-related aspects including production, technology selection, distribution routes, and storage, among others. It also introduces a multi-period comprehensive mathematical model that assists decision makers in jointly optimizing a multitude of decisions pertaining to the water supply chain, ranging from strategic to tactical ones. In particular, the former address the installation of new desalination plants along with their operational capacity, capacity expansion of existing plants and infrastructure assets (storage and distribution), as well as the selection of the best-suited desalination technologies. On the other hand, tactical decisions consider issues such as the allocation of water resources among end users, production level of desalinated water at the different plants, and storage levels across various demand zones. All these decisions are being optimized in every period towards minimizing financial and environmental costs throughout the planning horizon. To illustrate the model’s practical relevance and assess its validity, a case study focused on an Emirate in the United Arab Emirates (UAE). Results highlight the need for increased desalination capacity over the next 15 years to match growing demand. The study pinpoints the timings for desalination facility expansions, compensating for decreased capacity due to degradation or retirement. The study underscores the superiority of reverse osmosis technology over other desalination options.