Background <p>Reviews describing the occurrence of aspergillosis in newborns are sparse in the literature and mostly fragmented as case reports despite being a significant health challenge in this at-risk group. A review published in 1998 identified 44 cases, and to date, there is no comprehensive study highlighting the burden of <i>Aspergillus</i> infection in this vulnerable group across the globe. We aimed to highlight the burden of <i>Aspergillus</i> infection in neonates, the spectrum of clinical presentation and treatment outcomes.</p> Materials and Methods <p>We conducted a systematic literature search of the PubMed database from 1997 to December 2024 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guideline and adhered to the PRISMA checklist to identify articles reporting <i>Aspergillus</i> infection in neonates. The search terms were (<i>Aspergillus</i> OR Aspergillosis) AND (newborn OR neonates).</p> Results <p>We identified 48 cases reported globally. Europe had the highest reported cases (<i>n</i> = 22, 45.8%), followed by the United States of America (<i>n</i> = 12, 25.0%), then Asia (<i>n</i> = 12, 25.0%) and South Africa (<i>n</i> = 2, 4.2%). The spectrum of clinical presentations were cutaneous aspergillosis (<i>n</i> = 21, 43.8%), invasive aspergillosis (<i>n</i> = 15, 31.8%), pulmonary aspergillosis (<i>n</i> = 8, 16.70%), renal aspergillosis (<i>n</i> = 1, 2.1%), aspergillosis ventriculitis (<i>n</i> = 1, 2.1%), brain abscess (<i>n</i> = 1, 2.1%) and ethmoidal sinus aspergillosis (<i>n</i> = 1, 2.1%). Diagnostic methods deployed were mostly culture (<i>n</i> = 39, 81.3%), followed by histopathology (<i>n</i> = 19, 39.6%). Other diagnostics deployed were <i>Aspergillus</i> galactomannan assay (<i>n</i> = 14, 29.2%), Beta-D-glucan assay (<i>n</i> = 1, 2.1%) and microscopy (<i>n</i> = 6, 12.5%). Outcomes were stated in forty-seven cases: twenty-four neonates (51.5%) recovered, and twenty-three (48.9%) were fatal. Fatal outcomes were predominantly associated with multiple organ failure (<i>n</i> = 10, 43.5%). Other causes of mortality were respiratory distress/failure (<i>n</i> = 5, 21.7%), disseminated intravascular coagulopathy (<i>n</i> = 3, 13.0%), circulatory/cardiovascular failure (<i>n</i> = 2, 8.7%), non-resolving pneumonia (<i>n</i> = 1, 4.3%), septic shock (<i>n</i> = 1, 4.3%), post-surgery (<i>n</i> = 1, 4.3%) and pulmonary haemorrhage (<i>n</i> = 1, 4.3%).</p> Conclusion <p>Aspergillosis in the newborn is life-threatening and associated with fatal outcomes. A fatality rate of 48.9% reported in this review is alarming and informs the need to deploy infection control strategies geared towards reducing the risk of aspergillosis in the neonatal age group. In addition, cognizance is seemingly low as reports are sparse, especially from Africa and Asia. Adequate knowledge of the predisposing factors and a heightened index of suspicion on the part of the attending clinician are pertinent for the prompt identification of cases and good clinical outcomes. Also, an improved diagnostic infrastructure ensuring the routine availability of fungal diagnostics, particularly in resource-limited settings, and the means to perform susceptibility testing and the accessibility to appropriate antifungals are sacrosanct.</p>