Background: Neonatal mortality continues to be a public health problem globally. Sub-Saharan African countries continue to record high figures, recording almost 1 million neonatal deaths annually over 30 years. This makes it the only SDG region without decreasing neonatal deaths between 1990 and 2019. The neonatal mortality burden in Ghana is unevenly distributed, with the Eastern Region recording an increase in deaths per 1000 live births. This study examined admission into the neonatal intensive care unit to understand the conditions and factors contributing to neonatal admission and deaths in the region. Methods: A cross-sectional study design was used to gather data on admissions to the neonatal intensive care unit from 2017 to 2020. Variables used for statistical analysis and inferences included gender, age of neonates, maternal employment, education, principal diagnosis on admission, treatment outcome, and the mother's National Health Insurance Scheme status. Results: The study's leading causes of neonatal admission included, infections, neonatal sepsis and jaundice, birth asphyxia, macrosomia, prematurity, and pneumonia. Neonatal and maternal factors were not important determinants of neonatal mortality at the neonatal intensive care unit. On the other hand, having a valid National Health Insurance Scheme significantly mitigates the likelihood of neonatal death. Conclusions: Neonatal mortality remains a public health concern in Ghana. Based on the findings, it is recommended that there should be efforts to decrease prematurity and neonatal infections such as sepsis and birth asphyxia. Again, the hospital should increase the skills of its staff in handling these morbidities to increase the survival rate.