Background: Advances in technology, data availability, and analytics have helped improve quality of care in the neonatal intensive care unit. Objective: To provide an in-depth review of artificial intelligence (AI) and machine learning techniques being utilized to predict neonatal outcomes. Methods: The PRISMA protocol was followed that considered articles from established digital repositories. Included articles were categorized based on predictions of: (a) major neonatal morbidities such as sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity; (b) mortality; and (c) length of stay. Results: A total of 366 studies were considered; 68 studies were eligible for inclusion in the review. The current set of predictor models are primarily built on supervised learning and mostly used regression models built on retrospective data. Conclusion: With the availability of EMR data and data-sharing of NICU outcomes across neonatal research networks, machine learning algorithms have shown breakthrough performance in predicting neonatal disease.