BackgroundFrailty and self-management are important determinants of quality of life in cancer patients. However, their synergistic effects and potential mechanisms on quality of life in middle-aged and older adult postoperative gynecologic malignancy patients have not been adequately studied.ObjectiveThis cross-sectional study aimed to explore the relationship between frailty, self-management, and quality of life in middle-aged and older adult postoperative gynecologic malignancy patients.MethodsA cross-sectional study was conducted from January 2024 to April 2024 in three gynecological wards of a tertiary hospital in Wuxi. The study recruited 177 patients aged 45 years or older who underwent surgery for gynecologic malignancies (cervical, ovarian, and endometrial cancer). Data were collected using demographic and clinical characteristics, the Edmonton Frailty Scale, the Self-Management Competence Scale, and the EORTC Core Quality of Life Questionnaire. Structural equation modeling was used to explore the interactions between frailty, self-management, and quality of life.ResultsThe prevalence of frailty in middle-aged and older adult postoperative gynecologic malignancy patients was 39.5%, with a mean total self-management score of 125.81 ± 13.21 and a mean total quality of life score of 69.26 ± 10.88. The fit indices of the model indicated a good fit, and that frailty had multiple effects on quality of life; specifically, frailty could affect the quality of life directly or through self-management, i.e., self-management partially mediated frailty and quality of life.ConclusionSelf-management is a mediating variable between frailty and quality of life, suggesting that clinical workers can intervene in self-management skills to improve patient’s quality of life and physical and mental health.