In order to reduce the energy cost while improving the process operation, a study which aims to analyze the influence of the operational parameters variations and determine the optimal operating conditions of a pilot multi-effect desalination system (MED) at CIEMAT-Plataforma Solar de Almerıía (PSA) has been performed. An equation-based object-oriented mathematical model of the experimental MED plant, implemented using the modeling language Modelica and previously developed, calibrated and validated, has been adapted to carry out this study. Firstly, an energetic and exergetic analysis of the process under nominal conditions has been carried out, revealing the key sources of energy and exergy consumption. On the one hand, the thermal energy contained in the mass outflows are the main responsible source of the high energy consumption, on the other hand the entropy generation and the heat exchanged with the environment are the responsible of the exergy degradation. Secondly, a study on the influence of the operational parameters shows that the production of the real plant under nominal conditions is far from the maximum simulated values and some operational parameters have not a great influence in the process with respect to the rest. Finally, using a genetic optimization algorithm implemented in the modeling tool, a optimization process taking into account different energy and exergy performance criteria, sets optimal operational set points. •An energetic and exergetic analysis of the MED process has been carried out.•The key sources of energy and exergy consumption have been revealed.•Optimization according genetic algorithms has been carried out.•Optimization takes into account different energy and exergy performance criteria.