Neonatal sepsis is a blood-stream infection that affects newborns under the age of 28 days. Sepsis is common in NICUs and has a high prevalence of Klebsiella species. As a result, the study aims to find the antibiotic resistance profile, virulence factors, and the prognosis of K. pneumoniae-infected neonates. A prospective study was conducted which included 140 neonates with clinical sepsis. Characterization of Klebsiella pneumonia isolates was done by conventional methods. Drug resistance and virulence factors were detected by phenotypic methods. Genotypic methods included 16s rRNA amplification and sequencing. Detection of multidrug-resistant genes by PCR was performed. K. pneumoniae (26.9%) was the most common pathogen isolated. A high prevalence of ESBL was detected (58.8%). The prevalence of CRKP and MβL was about 29.4%, and 23.5% respectively. Two strains were Strong biofilm producers and nine isolates showed Beta hemolysis.7 strains were positive for the string test. Four strains were positive for the wcaG gene. 3 positive for magA (K1) and 2 were for gene wzy (K2). Three isolates carried blaCTX–M, four isolates harbored blaVIM, two for IMP, and one for NDM and KPC gene. K. pneumoniae isolates in the NICU increased in frequency and antibiotic resistance. It is a serious hazard to the healthcare system, and it necessitates strict infection control methods in healthcare settings, as well as antibiotic stewardship to prevent the overuse of antibiotics in neonatal sepsis.