AbstractBacteria‐induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self‐implantable core–shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH‐responsive antimicrobial nanoparticles (NPs), Ag@ZIF‐8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti‐angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF‐8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core–shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti‐angiogenic and anti‐inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.