Dynamic environment imposes such conditions that make it necessary for companies to consider sources of uncertainty in designing core business processes and optimizing supply chain operations. Efficient management of a supply system requires an integrated approach towards various operational functions and related source of uncertainties. Uncertain conditions in supply network design problem such as market demands, delivery time, and facility capacity are considered and incorporated by many studies at the mathematical programming formulations as well. In this chapter, extensive review of existing SCND literature, brief overview and classification on uncertainty sources, useful strategies to deal uncertainties, model formulation with uncertain/stochastic parameters, efficient developed solution methodologies, and improvement adjustment mechanisms are discussed. Lastly, some directions for further research in this area are suggested.