This paper discusses an enhanced use of Modeling and Simulation (M&S) in the design cycle of large scale infrastructure systems. After a short review of the use of M&S in the current systems design process, we identify some issues in multi-actor design environment. A Simulation Based Design (SBD) framework is proposed to tackle these issues using a multi-methodological approach. The framework is specified with formal description, and the tree-like structuring and refinement of design alternatives are explained. A case of applying the framework to container terminal design is presented and the evaluation is reported.