Insecticides remain one of the most efficient tools for pest control. However, their intensive use can lead to the expansion of the resistant populations, resulting in failed insecticide performance in the field. While insufficient, the insecticides still exert selection pressure on the pest population, altering their environmental adaptation. However, most studies on the environmental effects of resistant insect populations have primarily focused on fitness costs and cross-resistance in the absence of original insecticides. To address this gap, we conducted a study to monitor the physiological and xenobiotic responses of resistant insects after unsuccessful insecticide treatment. Specifically, we used an artificial chlorantraniliprole-resistant Drosophila melanogaster strain, created by editing the target gene (RyR) to mimic a natural occurring resistant mutation in the rice pest Chilo suppressalis. Our analysis primarily focused on the xenobiotic response genes in the CsRyRY4667D fruit flies following exposure to chlorantraniliprole through either feeding or contact. We found that the climbing ability, desiccation resistance, and thermal resistance of the CsRyRY4667D flies were affected by chlorantra-niliprole exposure. Contact-based chlorantraniliprole exposure resulted in flies becoming crosstolerant to the insecticide imidacloprid. Moreover, in responding to chlorantraniliprole, CsRyRY4667D flies also showed changes in the expression of genes responsible for detoxification enzymes and JNK signaling pathway, all of which appeared to be unaffected in the sensitive wild-type flies in our previous study. Our findings shed light on a previously overlooked aspect of ecological adaption in insecticide-resistant strains. They underscore the importance of understanding how resistant populations adapt to environmental pressures, which can have implications for more effective pest management strategies.