The lack of fresh water in the world has become a growing concern. As an open-source incremental technology for water resources, desalination has become an important method to solve the global water crisis. Based on the inherent safety, versatility, modularity, and advantages of high-temperature gas-cooled reactors, the Saudi Arabia desalination project is the relying background. This paper proposes a complete solution for the high-temperature gas-cooled reactor power and water coproduction project by selecting a combination of process-proven multi-effect distillation (MED) and reverse osmosis (RO). In the scheme, a tertiary circuit is designed for the isolation of radioactive entities. An innovative comparative analysis of the engineering investment and production costs of different desalination technologies, such as MED and RO, and a comparison of the investment estimates of the “thermal” and “membrane” methods for the production of 10,000 tonnes of fresh water per day are performed. The feasibility and energy efficiency of the multi-effect distillation–reverse osmosis (MED-RO) scheme are presented, demonstrating the feasibility and practicality of the above approach.