Background: Intraosseous (IO) access serves as a viable rescue route during neonatal resuscitation when umbilical venous catheterization proves difficult; however, evidence supporting its clinical applicationremains insufficient. Objective: To systematically evaluate the clinical application, efficacy , and safety rofile of IO access in neonates, thereby providing evidence to inform clinical practice Methods: A systematic search of Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL Complete, the Cochrane Library , and SinoMed was conducted from database inception to February 28, 2025. Studies reporting IO access in neonatal populations were included. Primary outcomes were first-attempt success, overall success, and complication rates. Results: Of 2,616 screened records, 18 studies comprising 329 neonatal patients were included (12 case reports, 4 case series, and 2 cross-sectional surveys). The youngest patient was 1 day old. Indications were predominantly respiratory (51.4%) and circulatory (26.8%) conditions. Devices used were powered (73.9%), manual (24.9%), and spring-loaded (1.2%), with the proximal tibia as the main insertion site (96.0%). The first-attempt success rate was 72.9% (156/214), and the overall success rate was 80.9% (199/265). Among 320 IO procedures with documented safety outcomes, the overall complication rate was 24.1%, including extravasation/infiltration (17 .3%) and soft-tissue ischemia/necrosis (2.5%). One case of compartment syndrome and one case of extravasation-related necrosis ultimately required amputation. Conclusion: Neonatal IO access achieves an overall success rate of approximately 81% but carries a clinically significant complication burden (24.1%), including rare limb-threatening events. IO placement should therefore be considered only in lifethreatening neonatal emergencies when alternative vascular access cannot be rapidly established.