Chronic wound healing is a major challenge in biomedicine. Conventional therapies are usually associated with poor drug permeability, low bioavailability, risk of antimicrobial resistance, and require frequent administration. Therefore, a novel formulation with reduced antibiotic dosage, improved drug delivery efficiency, and low application frequency is of remarkable interest for chronic wound healing. Herein, a multifunctional microneedle (MN) patch is presented to achieve rapid wound healing via efficient chemo-photodynamic antibacterial effect and sustained release of growth factors at the wound bed. When the MN patch pierces the skin, MN tips carrying both low dosage of antibiotics and bioactive small molecule-encapsulated metal-organic frameworks (MOFs) rapidly dissolve and subsequently deliver the payloads to the wound. Upon light irradiation, MOF-based nanoparticles robustly convert O 2 into 1 O 2 , which acts synergistically with chemotherapy to remove pathogenic bacteria from the wound, exhibiting excellent chemo-photodynamic antibacterial performance with a tenfold reduction in the required antibiotic amount. The nanoparticles can achieve a continuous release of growth factors in the wound tissue, promoting the formation of epithelial tissue and neovascularization, thereby further accelerating chronic wound healing. Collectively, the designed multifunctional MOF-based MN patches offer a simple, safe, and effective alternative for chronic wound management.