Acinetobacter baumannii is a significant nosocomial pathogen, particularly in critically ill patients, due to its ability to develop resistance to multiple antimicrobial agents. The increasing prevalence of carbapenem-resistant A. baumannii (CRAB) has made it a critical public health and clinical concern. Current antimicrobial agents are becoming less effective due to the bacterium's resistance mechanisms, including the production of β-lactamases, efflux pumps, and modifications of antibiotic target sites. A. baumannii's genetic adaptability allows it to acquire and disseminate resistance genes through plasmids, transposons, and integrons, contributing to its resilience. Biofilm formation further enhances its survival and resistance to antibiotics and immune responses. The review highlights the need for new therapeutic approaches, including combination therapies such as sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, and xeruborbactam, which target resistance mechanisms. Phage therapy and the use of artificial intelligence and deep learning are also being explored as complementary strategies. The development of new antimicrobial agents and strategies to inhibit resistance mechanisms, such as efflux pump inhibitors and β-lactamase blockers, are crucial for treating A. baumannii infections. The review emphasizes the importance of a coordinated global response to address the growing threat of antibiotic resistance caused by A. baumannii.Acinetobacter baumannii is a significant nosocomial pathogen, particularly in critically ill patients, due to its ability to develop resistance to multiple antimicrobial agents. The increasing prevalence of carbapenem-resistant A. baumannii (CRAB) has made it a critical public health and clinical concern. Current antimicrobial agents are becoming less effective due to the bacterium's resistance mechanisms, including the production of β-lactamases, efflux pumps, and modifications of antibiotic target sites. A. baumannii's genetic adaptability allows it to acquire and disseminate resistance genes through plasmids, transposons, and integrons, contributing to its resilience. Biofilm formation further enhances its survival and resistance to antibiotics and immune responses. The review highlights the need for new therapeutic approaches, including combination therapies such as sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, and xeruborbactam, which target resistance mechanisms. Phage therapy and the use of artificial intelligence and deep learning are also being explored as complementary strategies. The development of new antimicrobial agents and strategies to inhibit resistance mechanisms, such as efflux pump inhibitors and β-lactamase blockers, are crucial for treating A. baumannii infections. The review emphasizes the importance of a coordinated global response to address the growing threat of antibiotic resistance caused by A. baumannii.