The bacterium Acinetobacter baumannii (A. baumannii) poses a severe clinical challenge due to its high drug resistance, driven by genetic adaptability, biofilm formation, enzymatic degradation, and facilitating healthcare-associated infections. In our present study, we described and to developed an innovative strategy for A. baumannii pneumonia using multidrug codelivery of curcumin nanosuspensions and sulfamethoxazole (SZ) with polymyxin B (PB) (CNS@SZ/PB). The physicochemical properties, drug release kinetics, antibacterial efficacy, and anti-biofilm activity of CNS@SZ/PB were comprehensively evaluated. In-vitro anti-bacterial analysis of CNS@SZ/PB exhibited potent bacterial inhibition against A. baumannii with a minimum inhibitory concentration (MIC) of 60 μg/mL, it also effectively prevented biofilm formation at 50 μg/mL. Furthermore, the pediatric pulmonary targeting ability of CNS@SZ/PB demonstrated effective moderation of lung inflammation, offering a promising way for managing pulmonary-associated diseases. In-vivo studies on mice infected with multidrug-resistant A. baumannii validated the significant protective effects of CNS@SZ/PB, attributed to its regulation of inflammatory factors. Overall, our findings highlight the therapeutic potential of CNS@SZ/PB as a promising approach for combating A. baumannii infections, providing a solid foundation for further experimental analysis of pediatric pulmonary inflammation and disease.