<p>Postoperative recurrence and infection continue to pose major challenges after tumor resection. To address these, we developed a multifunctional nanocomposite hydrogel, designated as Gel@CAR-M@Mn@ELE. It is constructed by encapsulating CAR-M@Mn@ELE and immunomodulatory/antibacterial <i>Dendrobium officinale</i> polysaccharide (DOP) within a quaternary ammonium-modified gelatin methacryloyl hydrogel matrix. The CAR-M@Mn@ELE not only loads elemene (ELE) into porous Mn nanozymes (Mn NPs) but is also coated with EpCAM-targeting chimeric antigen receptor-engineered 293T cell membranes (CAR-M). Notably, through multiple modifications, the catalytic activity of Mn NPs has been preserved. In vitro studies demonstrated that CAR-M@Mn@ELE selectively targeted and killed 4T1 cancer cells (EpCAM⁺), while the hydrogel exhibited potent antibacterial activity against <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>). In vivo evaluation using a post-tumor-resection mouse model confirmed that Gel@CAR-M@Mn@ELE significantly suppressed tumor recurrence and prolonged survival. The combination of bioactive components within the hydrogel modulated the immunosuppressive tumor microenvironment, thereby enhancing its immunotherapeutic efficacy. Additionally, in a bacterial wound infection model, the hydrogel effectively inhibited bacterial growth and accelerated wound healing. The Gel@CAR-M@Mn@ELE offers a novel and promising strategy, supported by experimental evidence, for concurrently addressing the critical post-surgical challenges of tumor recurrence and wound infection.</p> Graphical Abstract <p></p>