The increasing presence of employed women undergoing menopause has stimulated a growing corpus of research highlighting the complex relationship between menopause and work. Nevertheless, little is known regarding the mechanism by which menopause affects work ability and work-related well-being. In order to fill this gap in the literature, the present study examined whether and how menopausal symptoms affect the relationship between job demands, work ability, and exhaustion. In total, 1,069 menopausal women employed as administrative officers in a public organization filled out a self-report questionnaire. A moderated mediation analysis was carried out using latent moderated structural (LMS) equation. The findings of this analysis indicated that the indirect effect of work ability on the relationship between job demands and exhaustion is influenced by the exacerbating effect of menopausal symptoms on the relationship between job demands and work ability. Moreover, the conditional effect confirmed that women with high menopausal symptoms receive more exposure to the negative effects of job demands on work ability compared to women with low menopausal symptoms. The present findings may help in addressing interventions to prevent negative outcomes for menopausal women and their organizations.