The emergence of infections caused by Acinetobacter baumannii, a multidrug-resistant bacterium, has been a concern worldwide. This bacterium is an important hospitalacquired pathogen that causes several diseases including ventilator-associated pneumonia, bloodstream infections, and meningitis. This study aimed to determine antibioticresistant mechanisms in the pathogenesis of A. baumannii and the alternative treatment strategies against it. The combined actions of outer membrane protein A, formation of a biofilm on biotic and abiotic surfaces, phospholipases C and D, metal homeostatic system, lipopolysaccharides, and verotoxins are relevant for virulence and pathogenesis. A. baumannii resists the broad-spectrum antibiotics by its mechanisms of resistance, such as β-lactamases, efflux pump, aminoglycoside modifying enzymes, permeability changes, and alternation of targets. In an attempt to overcome the resistance mechanisms, plant-derived compounds and a combination of the antibiotics and the plant phytocompounds have been focused. Nanoparticles synthesised with the plant extract have been studied extensively. Furthermore, we projected modern methods, including multi-omics analysis, to study insight into mechanisms of actions of antibiotics. The information suggested that the potential antibiotic mechanisms of A. baumannii could lead to an alternative treatment against A. baumannii infections.