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Abstract Background Acinetobacter baumannii (A. baumannii) is a life-threatening and challenging pathogen. In addition, it accounts for numerous serious infections, particularly among immunocompromised patients. Resistance to nearly all clinically used antibiotics and their ability to spread this resistance is one of the most important concerns related to this bacterium. Objectives This study describes different molecular mechanisms of two multidrug-resistant A. baumannii isolates obtained from endotracheal aspirates collected from the neonatal intensive care unit (NICU), Ain Shams University Hospital, Egypt. Methods Following the identification of two isolates, they were examined for susceptibility to antimicrobial agents. This was followed by multilocus sequence typing as well as whole-genome sequence (WGS). Additionally, a Pathosystems Resources Integration Center (PATRIC) analysis was performed. Results Two isolates, Ab119 and Ab123, exhibited resistance to all tested antibiotics except for tigecycline and colistin. The WGS analysis of antimicrobial resistance genes (AMR) indicated that both isolates shared beta-lactam, aminoglycoside, macrolides, and sulfonamide resistance genes. Furthermore, each strain revealed different resistance genes such as blaNDM-1, blaNDM-10, OXA-64, aph (3')-VI, Tet-B in Ab119 strain and blaOXA-68, blaPER-1, blaPER-7, Tet-39 in Ab123 strain. Multiple efflux pump genes were detected. Multilocus sequence typing indicated that both isolates belong to the same sequence type (ST931), which belongs to international clone (IC3). Both isolates exhibited the presence of multiple mobile genetic elements (MGEs), but no plasmid was detected in either of them. Conclusions A low prevalence of the IC3 sequence type was identified among two A. baumannii isolates obtained from the NICU in Egypt, exhibiting a high resistance level. Healthcare workers must have knowledge regarding the prevalence of A. baumannii among different populations in order to administer suitable treatment, improve patient outcomes, and apply effective infection control practices.