Although Conogethes punctiferalis and Conogethes pinicolalis have reported on morphology and molecular identification, the molecular biology differences between the two species in different diets are still unknown. In this work, we investigated the difference in the biological process of the two species by the methods of transcriptomics, proteomics, metabolomics, and bioinformatics. The results showed that the expression of 74,611 mRNA in the transcriptome, 391 proteins in the proteome, and 218 metabolites in the metabolome had been significantly changed between the two species, and the KEGG results showed the data were mainly closely related to metabolism and redox. Moreover, based on integrating system-omics data, we found that the α-amylase and CYP6AE76 gene have mutations between the two species. Different sequence analysis results may differ significantly in their exact substrate preference and product profile, which indirectly leads to the different detoxification or metabolism ability, and the gene expression of relevant was also confirmed by the qPCR and enzyme activity test. These findings in the two species and integrated networks provide beneficial information for further exploring the molecular mechanism of polyphagous and oligophagous.