Multi-Source Systems combining renewable energy sources with diesel generators have been widely adopted in isolated sites. The economic and ecological aspects are very important for analyzing and evaluating such systems. In this paper, an optimization approach that includes the former aspects has been proposed. This approach takes into account the changes in the fuel cost over a lifecycle and the minimization of the greenhouse gas emission. The proposed method is based on three main steps. At first, a fuel cost progression model over a period of 40 years has been developed. Second, due to the complexity of such systems and in order to simplify the modeling, meta-models have been extracted by using the Design of Experiments technique. Finally, Single Objective and Multi-Objective Optimization of the system based on economic and ecological criteria have been performed. The obtained results show that, changes in fuel costs have a significant influence on the sizing of the system. Indeed, the increase in fuel cost can lead to an increase of 18% in the design cost. The best solution on Pareto's curve was found with a reduction rate in the fuel consumption between 30 and 35%. Furthermore, the optimization algorithm favors the introduction of renewable sources.