<p>The house fly, <i>Musca domestica</i>, is a major mechanical vector of several pathogens, posing significant public health risks. Due to the hazards associated with indoor use of synthetic insecticides, biopesticides offer an eco-friendly alternative. Clove (<i>Syzygium aromaticum</i>) flower bud extract contains bioactive insecticidal compounds; however, a comprehensive study of its sublethal effects on <i>M. domestica</i>, along with the associated molecular responses, was lacking. Ethanol-based clove extracts were characterized using gas chromatography–mass spectrometry (GC-MS). This study assessed the lethal and transgenerational effects of clove extract on two generations using age-stage, two-sex life table analysis. Gene expression analysis was conducted on three key stress-responsive genes (<i>CYP12A2</i>, <i>CYP6D2</i>, <i>CYP6A24</i>) and one fecundity-related gene, vitellogenin<i>-</i>I (<i>Vg-I</i>). GC-MS analysis identified eugenol (68.80%), caryophyllene (13.24%), and acetyl eugenol (13.56%) as the major constituents. The lethal concentrations were determined as LC₅ = 0.405%, LC₅ = 1.574%, and LC₅₀ = 4.046%. The LC₅₀ treatment significantly reduced longevity, fecundity, and survival. Mean generation time (<i>T</i>) was significantly shorter in the LC₅₀ group (16.43 days) than in the control (19.89 days). Similarly, key population parameters—intrinsic rate of increase (<i>r</i>), finite rate of increase (<i>λ</i>), and net reproductive rate (<i>R</i>_<i>0</i>)—were reduced. Gene expression studies revealed elevated stress responses and reproductive suppression. The detoxification genes (<i>CYP12A2</i>, <i>CYP6D2</i>, <i>CYP6A24</i>) were upregulated, while the fecundity-related gene <i>Vg-I</i> was downregulated. Molecular docking suggested strong binding affinity of caryophyllene to survival-related proteins. These findings suggest that clove extract significantly affects <i>M. domestica</i>, highlighting the potential of caryophyllene as an insecticidal compound.</p>