Compression−absorption cascade refrigeration system (CACRS) is the extension of absorption refrigeration system, which can be utilized to recover excess heat of heat exchanger networks (HENs) and compensate refrigeration demand. In this work, a stage-wise superstructure is presented to integrate the generation and evaporation processes of CACRS within HEN, where the generator is driven by hot process streams, and the evaporation processes provide cooling energy to HEN. Considering that the operating condition of CACRS has significant effect on the coefficient of performance (COP) of CACRS and so do the structure of HEN, CACRS and HEN are considered as a whole system in this study, where the operating condition and performance of CACRS and the structure of HEN are optimized simultaneously. The quantitative relationship between COP and operating variables of CACRS is determined by process simulation and data fitting. To accomplish the optimal design purpose, a mixed integer non-linear programming (MINLP) model is formulated according to the proposed superstructure, with the objective of minimizing total annual cost (TAC). At last, two case studies are presented to demonstrate that desired HEN can be achieved by applying the proposed method, and the results show that the integrated HEN-CACRS system is capable to utilize energy reasonably and reduce the total annualized cost by 38.6% and 37.9% respectively since it could recover waste heat from hot process stream to produce the cooling energy required by the system.