The use of cold energy should be systematically integrated with process streams in low-temperature systems for energy savings and sustainable low-carbon society. In this paper, new design methodology for cascaded mixed refrigerant systems with multistage heat exchanges has been proposed, which systematically screens, evaluates and optimizes key decision variables in the design of refrigeration cycles (i.e. economic trade-off, partition temperature, refrigerant compositions, operating conditions, refrigerant flowrate). The integrated design and optimization for overall cryogenic energy systems is also addressed to reflect system interactions between driver selections and design of refrigeration systems. Two case studies are illustrated to demonstrate the advantage using developed design methods.