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[Display omitted] • A predictive model of a natural vacuum solar desalination system is proposed. • The model is verified by comparison with experimental results. • Annual freshwater yield of system in 2021 is up to 30.86 t/year in Chennai. • Thermal and total efficiency of system in 2021 peak at 79.41% and 76.96% in June in Muscat. • The freshwater cost of system in 2021 is as low as 5.31 $/t in Jizan. Solar-powered desalination systems have attracted much attention because they can alleviate freshwater shortages without polluting the environment. In the present work, a mathematical model is established to estimate the performance of a natural vacuum solar desalination system via water-filling and air-releasing. The estimates are compared with experimental results to validate the model. Six typical Asian cities are selected as the potential locations for the system. The annual freshwater yield, efficiency, and freshwater cost of the system are estimated for these cities under 2021 weather conditions to predict its productivity and commercial prospects. The results show that the average predictive error of the model is <3.52%. Jizan has the highest application potential among the six regions, with an all-day freshwater yield of about 10.77 kg/h and 55.96 kg/m3h on a typical day. The desalination system has a maximum annual freshwater yield of 30.86 t/year in Chennai, a maximum thermal efficiency of 79.41% and a maximum total efficiency of 76.96% in June in Muscat, and a minimum freshwater cost of 5.31 $/t in Jizan. Therefore, the predictive model is highly accurate and its results confirm the wide applicability and great commercial potential of the desalination system in Asia, potentially, the whole world. [ABSTRACT FROM AUTHOR]