<p>Pelvic floor dysfunction (PFD) in women is characterized primarily by the functional degeneration of pelvic support structures, with pelvic organ prolapse (POP) being a common clinical manifestation. Current materials for repairing POP are limited by suboptimal mechanical performance and inadequate anti-inflammatory and antibacterial capabilities. Herein, a immunomodulatory piezoelectric master electrospun membrane is innovatively designed to provide integrated mechanical support, piezoelectric responsiveness, and immune microenvironment regulation. Electrospun membranes with uniformly loaded zinc oxide (ZnO) nanoparticles enabled the sustained release of Zn²⁺ for more than 20 days and achieved a piezoelectric coefficient (<i>d</i>_<i>33</i>) of 5.34 pm/V. The voltage output remained stable under mechanical stimulation cycles, and the ultimate tensile strength could reach 12.11&#xa0;MPa while maintaining sufficient ductility. In vitro, the immunomodulatory piezoelectric master electrospun membrane exhibited excellent biocompatibility, significantly promoted tube formation by human umbilical vein endothelial cells (HUVECs), and upregulating the expression of IL-4 and IL-10. Moreover, it effectively inhibited inflammatory cell infiltration, promoted orderly collagen deposition, stimulated angiogenesis and accelerated tissue repair when used in vivo to treat abdominal wall muscle defects in rats. Therefore, immunomodulatory piezoelectric master electrospun membrane provides a promising approach for advanced soft tissue regeneration with broad clinical significance.</p> Graphical Abstract <p></p>