The growth of consumer demand has greatly accelerated resource consumption, with significant impact on supply chain sustainability. How to improve the eco-efficiency and balance economic and environmental performance is a key to sustainable supply chain management. This chapter focuses on illustrating the application of the multi-criteria decision making (MCDM) in optimizing the eco-efficiency of the supply chain, including A data-driven multi-objective optimization modeling approach to reduce the inherent risk, carbon emission, and operational cost of hazardous materials flowing through the supply chain; A system dynamics modeling approach to simulate the recycling capacity of wastes in a closed-loop supply chain system for agro-products; and A multiple indicator system integrated with data envelopment analysis and fuzzy decision-making to assess the vulnerability of core production enterprises in a typical chemical product supply chain.