This work contributes to the debate on how uncertainty and concepts of sustainable development can be put into modern Supply Chain Network (SCN). First, we study the literature review, which is a review of the current state of the art of Supply Chain Network Design (SCND) approaches and resolution methods. Second, we propose a new methodology for multi-criteria SCND as well as its application to real SCN, in order to satisfy the customers demand and respect the environmental, social, legislative, and economical requirements. Third, we present a multi-objective model that captures a compromise between the total cost and the environment influence. After that, we develop a novel heuristic solution method based on decomposition technique, to solve large scale SCND problems. Finally, we use two-stage stochastic programming approach to model the SCN under demand uncertainty. Then, we address uncertainty in all SCN parameters, we use possibilistic linear programming approach to model the problem and we validate both approaches in a large application case.