The hybridization of desalination processes is one of the most promising technologies to overcome the current limitations of desalination technologies while maximizing the advantages of individual processes in practice. Multi-effect distillation (MED) and adsorption desalination (AD) hybrid desalination process has been investigated in this study to maximize the utilization of energy input in desalination. Two different thermal desalination technologies have been integrated, and the synergetic impact of utilizing energy enhanced the performance of the hybrid system. The synergetic thermodynamic model has been developed in this study and the experimental results from the pilot unit, with a nominal production capacity of 10 m3/day, installed at KAUST, KSA have been affirmed the proposed model. Both the water production and the universal performance ratio (UPR) have been improved 2–5 times in different quality of the heat source (40–60 °C) to the MED. Moreover, the MED-AD hybrid process is enabled to scavenge the energy from the ambient temperature below 30 °C for the desalination. The utilized energy of both thermal and flash evaporation in all operation conditions, and individual effects has been inventoried to analyze the thermodynamic synergy of the hybridization. In the sole MED operations, the energy input in the first effect is carried over to the following effects, and part of it is used for thermal evaporation. However, due to the AD driven flash evaporation, the energy used in evaporation of the following effect is shown greater than the previous effect. The developed synergetic model of MED-AD hybrid system and its experiment with 4-effects MED pilot have demonstrated the potential of the hybrid system and its application to the industrial processes.