This study presents a multifunctional liposomal polydopamine nanoparticle (MPM@Lipo) designed to combine chemotherapy, photothermal therapy (PTT), and oxygen enrichment for the treatment of rheumatoid arthritis (RA). MPM@Lipo effectively scavenges intracellular reactive oxygen species (ROS) and relieves joint hypoxia, promoting the repolarization of M1 macrophages into the M2 phenotype. In vivo studies in a rat adjuvant-induced arthritis model showed that MPM@Lipo accumulated in inflammatory joints, inhibited the production of inflammatory factors, and protected cartilage. Laser irradiation enhanced the temperature, leading to the destruction of excessive inflammatory cells and the acceleration of methotrexate (MTX) and oxygen production, resulting in excellent RA treatment effects. Overall, the synergistic chemotherapy/PTT/oxygen enrichment therapy using MPM@Lipo shows significant potential as a powerful strategy for RA treatment.This study presents a multifunctional liposomal polydopamine nanoparticle (MPM@Lipo) designed to combine chemotherapy, photothermal therapy (PTT), and oxygen enrichment for the treatment of rheumatoid arthritis (RA). MPM@Lipo effectively scavenges intracellular reactive oxygen species (ROS) and relieves joint hypoxia, promoting the repolarization of M1 macrophages into the M2 phenotype. In vivo studies in a rat adjuvant-induced arthritis model showed that MPM@Lipo accumulated in inflammatory joints, inhibited the production of inflammatory factors, and protected cartilage. Laser irradiation enhanced the temperature, leading to the destruction of excessive inflammatory cells and the acceleration of methotrexate (MTX) and oxygen production, resulting in excellent RA treatment effects. Overall, the synergistic chemotherapy/PTT/oxygen enrichment therapy using MPM@Lipo shows significant potential as a powerful strategy for RA treatment.