Aims & Objectives: Pulmonary overflow (PO) is a pathological condition that occurs in newborns with complex congenital heart diseases (CHD). Hypoxic gas therapy (HGT) is a therapeutic alternative where pulmonary vasoconstriction is induced through oxygen therapy with an inspired oxygen fraction less than 21%; the goal is to balance systemic and pulmonary blood flow in pre-surgical management. The objective of this systematic review is to assess the effectiveness of HGT in the preoperative management of PO in newborns with complex congenital heart diseases. Methods: A comprehensive search in PubMed/MEDLINE, Google Scholar, and the Cochrane Library targeted original articles assessing HGT in newborns with CHD before surgery. Two independent reviewers followed PRISMA guidelines, using ROBINS-I and RoB-2 tools for bias assessment. Qualitative synthesis was performed. Results: Nine publications (n=107 patients, 69.2% with hypoplastic left heart syndrome) were identified, revealing a high risk of bias due to lack of blinding and confounding variables. HGT with CO2 showed increased blood pressure, cerebral oximetry, oxygen saturation, and urinary output. No impact on lactate clearance was observed. HGT with nitrogen induced less hemodynamic change than CO2. No adverse events were reported.Conclusions: The therapeutic benefits of HGT in managing PO in complex CHD, particularly with CO2, seem to be evident. Nevertheless, the notable high risk of bias and the absence of well-controlled placebo trials raise concerns. Additionally, there is a lack of evidence regarding potential long-term adverse effects. Keywords: Congenital Heart Defects, Pulmonary Overflow, Newborn