This paper sets the foundation of the optimal design of most systems that use or produce heat and/or power including desalination, The separation process of the desalination technologies by membranes and by distillation is considered as an example for the purpose of clarity and for the special importance to desalination, Both the energetics and the economics of the separation process are based on a quantitative formulation of the second law of thermodynamics in terms of the concept of exergy and its destruction. The separation process is considered for five main desalination systems: reverse osmosis, electrodialysis, vapor compression, boiling evaporation and flash evaporation. Tile results of the energetic analysis show a dose competition between reverse osmosis and distillation for seawater desalination, The electrodialysis process is justified for the treatment of more dilute brackish water. It is shown that the determination of the driving force associated with exergy destruction occupies a central position in this comparison. The optimal design of the separation surface for minimum cost of energy and surface requirements takes off smoothly from the energetic analysis and sets the basis of a general and powerful approach to optimal system design. A second paper [1] is devoted to the general approach and its extension to cover almost all kinds of industrial processes and their combinations to produce one or more products.