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Simple Summary: Leguminivora glycinivorella, commonly known as the soybean borer, is one of the main pests in soybean production. Beauveria bassiana is an effective fungus for controlling the soybean borer. This study was based on soybean borer infected by Beauveria bassiana; combined transcriptome and metabolome analysis was performed. Three classes of antifungal differentially expressed genes were screened from the soybean borer, which were glutathione S-transferase (GSTs) genes, heat shock protein (HSP) genes, and cytochrome P450 (CYP450) genes. These three kinds of genes have an immune response in the pathway of glucose metabolism, lipid metabolism, and amino acid metabolism. These results provide a theoretical basis for improving the efficacy of Beauveria bassiana against soybean borer. According to the antifungal gene of soybean borer, we can develop a biological preparation to improve the control effect of Beauveria bassiana. This study utilized Beauveria bassiana to infect Leguminivora glycinivorella, analyzed the effects on the transcriptome and metabolome, and further investigated the antibacterial function of L. glycinivorella. We performed transcriptome and metabolome sequencing on the L. glycinivorella infected with B. bassiana and its control groups, and performed a joint analysis of transcriptome and metabolome results. Upon screening, 4560 differentially expressed genes were obtained in the transcriptome and 71 differentially expressed metabolites were obtained in the metabolome. On this basis, further integration of the use of transcriptomics and metabonomics combined an analysis of common enrichments of pathways of which there were three. They were glutathione S-transferase (GSTs) genes, heat shock protein (HSP) genes, and cytochrome P450 (CYP450) genes. These three pathways regulate the transport proteins, such as ppars, and thus affect the digestion and absorption of sugars and fats, thus regulating the development of pests. The above conclusion indicates that B. bassiana can affect the sugar metabolism, lipid metabolism, and amino acid metabolism pathways of L. glycinivorella, and can consume the necessary energy, protein, and lipids of L. glycinivorella. The research on the immune response mechanism of pests against pathogens can provide an important scientific basis and target for the development of immunosuppressants. This study laid an information foundation for the application of entomogenous fungi to control soybean borer at the molecular level. [ABSTRACT FROM AUTHOR]