Meconium ileus (MI) is the result of the accumulation of thick, dry, inspissated meconium that creates a bowel blockage, most commonly in the terminal ileum. These pockets of meconium prevent passage of stool beyond the point of obstruction, which leads to distention of the proximal bowel, bowel wall thickening, and distal microcolon. Occurring most commonly (90%) in conjunction with cystic fibrosis (CF), the occurrence of MI without CF is rare. The literature describes the incidence of MI associated with CF occurring in as many as 24.9% of those who have a pair (homozygous) of the most common CF gene mutation, Delta F508. The incidence of MI decreases with other CF mutations, of which there are over 2,000. The morbidity and mortality risks are related to whether the MI is simple or complex. Simple MI can be managed clinically with contrast enemas to relieve the obstruction and restore bowel function, while complex MI requires surgical intervention for possible bowel necrosis, perforation, peritonitis, strictures, and/or volvulus that can occur in utero or after birth. This article presents a case report of a 32-week-gestation female infant with gross abdominal distention beginning on day of life 1. The differential diagnosis, necessary testing, and required treatment that led to the final diagnosis will be presented. Additionally, radiographic modalities used to confirm the diagnosis are discussed. Finally, nursing management of the infant with simple or complex MI and short- and long-term challenges for infants and their families will be addressed.