Neonatal sepsis, a life-threatening condition, represents a critical challenge in the realm of Paediatric medicine, encapsulating a complex interplay of microbial invasion and host response in newborn infants within the first 28 days of life. The genesis of neonatal sepsis often originates from the vertical transmission of pathogens during pregnancy or exposure during the perinatal period, with the most susceptible cohort being preterm and low-birth-weight infants due to their underdeveloped immune systems. This multifaceted disorder manifests in two distinct forms: early-onset sepsis (EOS), typically occurring within the initial 72 hours postpartum, and late-onset sepsis (LOS), presenting beyond this timeframe and often associated with nosocomial infections. Clinical manifestations of neonatal sepsis encompass a spectrum of nonspecific signs, including lethargy, poor feeding, respiratory distress, and temperature instability, making prompt diagnosis a formidable challenge. The microbial landscape contributing to neonatal sepsis is broad, involving bacteria, viruses, and fungi, with Group B Streptococcus and Escherichia coli ranking prominently among the causative agents. The diagnostic arsenal incorporates blood cultures, inflammatory markers, and advanced imaging techniques, though their sensitivity and specificity remain subjects of ongoing refinement. The management of neonatal sepsis mandates swift initiation of empiric antibiotic therapy, often tailored to the prevailing local epidemiology, accompanied by meticulous supportive care encompassing respiratory and hemodynamic support. The prevention of neonatal sepsis hinges on prenatal screening, intrapartum antibiotic prophylaxis, and rigorous infection control practices within neonatal intensive care units. Despite advances in medical care, neonatal sepsis persists as a formidable global health concern, necessitating ongoing research endeavors to elucidate its pathophysiology, refine diagnostic strategies, and optimize therapeutic interventions, ultimately striving to mitigate the profound impact on neonatal morbidity and mortality.