Phototherapy is a low-risk alternative to traditional antibiotics against drug-resistant bacterial infections. However, optimizing phototherapy agents, refining treatment conditions, and addressing misuse of agents, remain a formidable challenge. This study introduces a novel concept leveraging the unique customizability of metal-organic frameworks (MOFs) to house size-matched dye molecules in “single rooms”. The mesoporous iron(III) carboxylate nanoMOF, MIL-100(Fe), and the hydrophobic heptamethine cyanine photothermal dye (Cy7), IR775, are selected as model systems. Their combination is predicted to minimize dye-dye interactions, leading to exceptional photostability and efficient light-to-heat conversion. Furthermore, MIL-100(Fe) preserves the antimicrobial nature of hydrophobic IR775, enabling it to disrupt bacterial cell envelopes. Through electrospinning, MIL-100(Fe)@IR775 nanoparticles are shaped into a gelatin-based film dressing for the treatment of skin wounds infected by Methicillin-resistant Staphylococcus aureus (MRSA). Activation of the dressing requires only a portable near-infrared light-emitting diode (NIR LED) and induces both low-dose photodynamic therapy (LPDT) and mild-temperature photothermal therapy (MPTT). Combined with the antimicrobial properties of IR775 and ferroptosis-like lipid peroxidation induced by MIL-100(Fe), the photoactive dressing eradicates MRSA and the healing is as quick as the uninfected wounds. This safe, cost-effective, and multifunctional therapeutic wound dressing offers a promising solution to overcome the current bottleneck in phototherapy.