Nowadays, desalination continues to expand globally, which is one of the most effective solutions to solve the problem of the global drinking water shortage. However, desalination is not a fail-safe process and has many environmental and human health consequences. This paper investigated the desalination procedure of seawater with different technologies, namely, multi-stage flash distillation (MSF), multi-effect distillation (MED), and reverse osmosis (RO), and with various energy sources (fossil energy, solar energy, wind energy, nuclear energy). The aim was to examine the different desalination technologies’ effectiveness with energy sources using three assessment methods, which were examined separately. The life cycle assessment (LCA), PESTLE, and multi-criteria decision analysis (MCDA) methods were used to evaluate each procedure. LCA was based on the following impact analysis and evaluation methods: ReCiPe 2016, IMPACT 2002+, and IPCC 2013 GWP 100a; PESTLE risk analysis evaluated the long-lasting impact on processes and technologies with political, economic, social, technological, legal, and environmental factors. Additionally, MCDA was based on the Technique for Order Preference by Similarity to the Ideal Solution (TOPSIS) method to evaluate desalination technologies. This study considered the operational phase of a plant, which includes the necessary energy and chemical needs, which is called “gate-to-gate” analysis. Saudi Arabia data were used for the analysis, with the base unit of 1 m3 of the water product. As the result of this study, RO combined with renewable energy provided outstanding benefits in terms of human health, ecosystem quality, and resources, as well as the climate change and emissions of GHGs categories.