ABSTRACT Introduction: Nosocomial pneumonias are the second most common healthcare-associated infections (HCAIs), often associated with the presence of Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter species, and Enterobacter species. Increasing use of carbapenems has led to an increase in the prevalence of carbapenem-resistant gram-negative organisms, such as carbapenem-resistant Enterobacterales (CRE), P. aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), limiting treatment options for patients at high-risk of multi-drug resistant (MDR) gram-negative pathogens. Areas covered: The purpose of this review is to discuss the role of meropenem/vaborbactam, a beta-lactam combined with a novel non-beta-lactam cyclic boronic acid beta-lactamase inhibitor (BLI), for the treatment of nosocomial pneumonia based on its chemistry, pharmacokinetics/dynamics, microbiological spectrum of activity, mechanisms of resistance, safety, and clinical efficacy. Expert opinion: Currently, any utilization of meropenem/vaborbactam beyond its FDA-approved indication for complicated urinary tract infections is considered off-label use; however, based on the pulmonary penetration of meropenem/vaborbactam, it is highly likely to be a safe and effective alternative to more toxic agents, like aminoglycosides and polymixins, for targeted therapy in pulmonary infections due to CRE. Unfortunately, the multifactorial resistance pattern of CRPA and other non-lactose-fermenting gram-negative bacteria restricts activity against these organisms which are common pathogens implicated in nosocomial pneumonia.