Intervention studies designed to improve neurodevelopmental outcomes of premature infants in the neonatal intensive care unit (NICU) were evaluated in this systematic review to analyze research methods, to illuminate the effectiveness of interventions, and to make recommendations for future research. Google Scholar, the Cumulative Index of Nursing and Applied Health Literature, PubMed, and Cochrane databases were investigated to identify experimental and quasi-experimental interventional studies in peer-reviewed journals. Each study was assessed in the areas of sample, design, interventional strategies, threats to validity, and outcomes. Nineteen articles were reviewed with a variety of clustered and individual strategies identified to improve neurodevelopmental outcomes of premature infants in the NICU. Developmental care in the NICU appears to have some positive effects on the neurodevelopment of preterm infants. However, there were a number of limitations identified that threaten the validity of the included studies. Going forward, components of developmental care should be operationalized more consistently, greater effort should be put into ensuring treatment fidelity, and electroencephalogram data should be collected in conjunction with behavioral outcome measures.