Background <p>The objective of this network meta-analysis was to evaluate and compare the efficacy and safety of different antimicrobial regimens used in the treatment of pneumonia caused by extensively drug-resistant (XDR) or multidrug-resistant (MDR) <i>Acinetobacter baumannii</i> (AB). Given the increasing prevalence of resistant strains, identifying optimal treatment strategies is crucial.</p> Materials and methods <p>We systematically analyzed data from randomized controlled trials and retrospective cohort studies retrieved from major electronic databases. The included studies evaluated all-cause mortality, clinical success, microbiological eradication, and nephrotoxicity associated with cefiderocol, intravenous (IV) colistin, inhaled colistin, igecycline, sulbactam, and their combination-based regimens in patients with MDR/XDR-AB pneumonia.</p> Results <p>A total of 19 eligible studies involving 1,941 participants were included in the analysis. Cefiderocol-containing regimens demonstrated the greatest reduction in all-cause mortality (odds ratio (OR): 0.24; 95% CI: 0.09–0.68) compared to other therapies. In terms of clinical success, cefiderocol-containing regimens (OR: 2.77; 95% CI: 1.07–7.19) and inhaled colistin (OR: 2.61; 95% CI: 1.14–5.99) were significantly more effective than other regimens. Microbiological eradication was most notable with inhaled colistin, and with IV colistin combined with sulbactam or tigecycline. However, nephrotoxicity was commonly observed with IV colistin, while tigecycline monotherapy showed the lowest nephrotoxicity risk (OR: 0.15; 95% CI: 0.04–0.60).</p> Conclusion <p>This study provides comprehensive evidence on current and emerging treatments for MDR/XDR-AB pneumonia. Cefiderocol-containing regimens appears to be the most effective regimen in reducing mortality and improving clinical outcomes, though nephrotoxicity risks must be carefully considered when using IV colistin-based therapies.</p> Clinical trial <p>Not applicable.</p>