Pantoea agglomerans, a gram-negative bacterium, has emerged as an opportunistic pathogen, particularly within neonatal healthcare settings. Initially perceived as an innocuous environmental contaminant, P. agglomerans has been increasingly implicated in a spectrum of clinical infections, including neonatal sepsis and bacteremia. This systematic review conducts an in-depth analysis of the clinical cases published in 2003-2023, elucidating the multifaceted clinical presentations and therapeutic challenges associated with P. agglomerans infections in neonates. In total, 11 case reports and case series of 45 neonates from eight different countries were included. Most of the infected patients (57.8%) were reported in Asian countries (Sri Lanka, India, Kuwait) and involved preterm neonates (64.4%) with extremely low to low birth weight, and concurrent medical conditions including co-infections in a few of them (15.6%). Blood was the main culture source of the pathogen, accounting for 42 cases (91.1%) whereas clinical presentations in neonates exhibited considerable heterogeneity, encompassing common symptoms such as feeding difficulties, respiratory distress, fever, lethargy, and sepsis. Neonatal survival largely depended on the infection's origin and the timing of diagnosis. Considering antibiotic susceptibility as a criterion for treatment selection led to a 74% survival rate. Usually, a combination of antibiotics was used. There were 11 neonatal deaths reported, leading to an estimated mortality rate of 24.4%. We conclude that outbreaks within neonatal intensive care units underscore the importance of stringent infection control practices and heightened surveillance, especially considering the rapid disease progression noted in the included studies. Enhanced awareness and understanding of the clinical and microbiological characteristics of P. agglomerans infections are paramount for optimizing outcomes and reducing the burden of disease in neonatal populations.