Tribolium castaneum (Herbst) is a major pest of stored products. Plant-derived essential oils are promising, eco-friendly alternatives for pest control. This study aimed to identify the active insecticidal components in Houttuynia cordata essential oils and to explore their modes of action against T. castaneum. Gas chromatography-mass spectrometry (GC-MS) identified 62 components, with 2-undecanone being the predominant constituent of the essential oil from the underground parts. Bioassays revealed that adults were more susceptible (LD50 = 8.84 μg/adult) than larvae (LD50 = 17.25 μg/larva). Integrative transcriptomic and proteomic analyses, supplemented by qPCR (quantitative polymerase chain reaction), PRM-targeted proteomics, and RNA interference (RNAi), were used to explore the mechanisms underlying the differential susceptibility. Omics analyses revealed that adults had suppressed immune and detoxification responses, with downregulation of SPH115 (immune-related serine protease) and CSP06 (phase 0 chemosensory protein). Conversely, larvae exhibited structural and metabolic defences, including the significant upregulation of cuticle-associated farnesol dehydrogenases (FDa, FDb) and detoxification enzymes (CYP6BQ7, GST). Silencing these genes via RNAi significantly increased larval mortality under 2-undecanone stress. These findings elucidate the stage-specific mechanisms of 2-undecanone toxicity, providing potential insights for developing targeted, environmentally safe botanical insecticides.