| Summary: | <i>Musca domestica</i> L., a pest of animals and humans, has developed resistance to alpha-cypermethrin, a pyrethroid insecticide commonly used to control medically important pests in many countries, including Saudi Arabia. We investigated the mechanism underlying the development of alpha-cypermethrin resistance and life history characteristics of alpha-cypermethrin–susceptible (Alpha-SS) and alpha-cypermethrin-resistant (Alpha-RS) <i>M. domestica</i> using the age-stage, two-sex life table theory, which is crucial for developing a future rational management strategy and minimizing the negative effects of alpha-cypermethrin on the environment. Our results showed that Alpha-RS <i>M. domestica</i> had a 405.93-fold increase in resistance to alpha-cypermethrin relative to Alpha-SS <i>M. domestica</i>. This increase in the resistance toward insecticide was attributed to metabolic enzymes, such as glutathione S-transferases, specific esterases, and cytochrome P450 monooxygenases. Furthermore, Alpha-RS <i>M. domestica</i> exhibited lower relative fitness (0.50), longevity, survival rate, life expectancy, reproductive values, intrinsic rate of increase, net reproductive rate, fecundity, maternity, and finite rate of increase, along with shorter larval, female preadult, and adult durations than Alpha-SS <i>M. domestica</i>, indicating fitness costs associated with most parameters. However, no significant differences were found between the strains in the following parameters: egg, pupa, and male preadult durations; adult preoviposition, total preoviposition, and oviposition periods; female ratio; and total generation time. Additionally, Alpha-RS <i>M. domestica</i> had a markedly lower intrinsic rate of increase, net reproductive rate, and finite rate of increase than Alpha-SS <i>M. domestica</i>. The results of this study suggest that alpha-cypermethrin resistance may lead to dominant fitness costs in <i>M. domestica</i>. Overall, these findings will aid in the development of rational control strategies for <i>M. domestica</i> as well as help to reduce pesticide pollution.
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