Finding optimal operating conditions of solar-based power and cooling systems is always a challenge. Performance of these systems is highly dependent on several important parameters, which influence not only the long-term efficiency but also its technical and economic feasibility. This paper studies the operation/configuration problem of an ammonia–water power and cooling cycle using an exergetic and statistical analysis. The Modeling developed in Matlab® and REFPROP 9.0 was used to calculate the thermodynamic properties of the ammonia–water mixture. The thermodynamic model and properties of the ammonia/water mixture were validated with previous models found in the literature. Optimal operating conditions of the combined cycle were obtained by using response surface technique and the ratio between exergetic efficiency and exergy destruction was used as response variable. The results showed that the response variable is highly influenced by the ammonia concentration, pressure ratio (PR), turbine efficiency, and pinch point temperature in the heat exchanger. Finally, the combined cycle was integrated with a solar field using two types of concentrated solar collectors.