The codling moth, Cydia pomonella(L.) (Lepidoptera: Tortricidae) is a major global pest of pome fruits, and it was considered a serious invasive species, threatening the safety of fruit production areas in Loess Plateau and Bohai Bay. The effective management of the codling moth mainly depends on chemical insecticides. However, a major problem associated with chemical control of the codling moth is the development of insecticide resistance worldwide. Among them, metabolic resistance is the main mechanism for C. pomonella resistance. To understand the metabolic mechanisms of insecticide resistance in C. pomonella, the molecular changes of detoxification enzymes were examined. Molecular simulation based methods can be important for such related research. This paper reviews the molecular simulation methods and its application in elucidating molecular metabolic mechanisms of insecticide resistance in C. pomonella. Future potential research directions using molecular simulation are put forward.