Rough oppositions in today’s global supply chain have forced business enterprises to focus attention on their supply chains. These issues have guided this research to introduce a qualitative measure to evaluate the reliability of any Supply chain network and develop a novel reliability-based robust design optimization approach to guarantee reliability requirements and minimize uncertainty impacts. A supply chain network design must maintain its efficiency over time while coping with the uncertainty in production and transportation. Analytical models for the determination of the risk involved in a supply chain network design are difficult to derive when uncertainty impacts are integrated. In this paper, a model of evaluating SCN is detailed first. Then, the methodology for the Reliability-based robust design optimization approach is provided. A case study is performed to demonstrate the effectiveness of the proposed Reliability measure and the developed Reliability-based robust design optimization model. Results from the case study have shown that by implementing the developed optimization approach, a SCN is able to achieve a 90% of required reliability while minimizing uncertainty impact.