Optimal supply chain design is vital to the success of industrial concerns now more than ever before. This paper reviews some principal research opportunities and challenges in the field of supply chain design. The growing area of enterprise-wide optimization and the increasing importance of energy and sustainability issues provide plentiful opportunities for supply chain design research. However, modeling, algorithmic, and computational challenges arise from these research opportunities. There are three major technical challenge areas where knowledge gaps can be addressed in supply chain design, namely multi-scale challenges, multi-objective and sustainability challenges, and multi-player challenges. This paper provides an overview of opportunity areas, a description of relevant technical challenges, and a perspective on how these challenges might be addressed in supply chain design. Illustrative examples are presented to illuminate avenues for future research. (c) 2015 Elsevier Ltd. All rights reserved.