This study presents a multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedle (MN) system for the treatment of MRSA-infected wounds. The MNs are designed to deliver HAZ@Fu nanoparticles, which are composed of hyaluronic acid (HA), fucoidan (Fu), and Zn-MOF. The HA coating enables subcellular targeting of MRSA, while Fu and Zn ions provide antibacterial activity, reduce inflammation, and promote tissue regeneration. The MNs are fabricated using a biocompatible gelatin methacryloyl (GelMA) hydrogel and a dissolvable polyvinyl acetate (PVA) backing layer. In vivo experiments on mice with MRSA-infected wounds showed that HAZ@Fu MNs significantly reduced bacterial load, accelerated wound healing, and promoted epithelial regeneration and neovascularization. The study also demonstrated that HAZ@Fu MNs effectively target MRSA within lysosomes, leading to enhanced therapeutic outcomes. The results suggest that the integration of HAZ@Fu NPs with biodegradable MNs could serve as a promising approach for the treatment of infected wounds. However, further research is needed to fully understand the underlying mechanisms and optimize the system for clinical applications.This study presents a multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedle (MN) system for the treatment of MRSA-infected wounds. The MNs are designed to deliver HAZ@Fu nanoparticles, which are composed of hyaluronic acid (HA), fucoidan (Fu), and Zn-MOF. The HA coating enables subcellular targeting of MRSA, while Fu and Zn ions provide antibacterial activity, reduce inflammation, and promote tissue regeneration. The MNs are fabricated using a biocompatible gelatin methacryloyl (GelMA) hydrogel and a dissolvable polyvinyl acetate (PVA) backing layer. In vivo experiments on mice with MRSA-infected wounds showed that HAZ@Fu MNs significantly reduced bacterial load, accelerated wound healing, and promoted epithelial regeneration and neovascularization. The study also demonstrated that HAZ@Fu MNs effectively target MRSA within lysosomes, leading to enhanced therapeutic outcomes. The results suggest that the integration of HAZ@Fu NPs with biodegradable MNs could serve as a promising approach for the treatment of infected wounds. However, further research is needed to fully understand the underlying mechanisms and optimize the system for clinical applications.