Inadequate intake of calcium and phosphorus during the perinatal period can result in metabolic bone disease (MBD), characterized by decreased bone mass, altered bone mineralization, and increased risk for fractures. Preterm neonates have higher risk of developing MBD. Treating MBD involves ensuring adequate calcium and phosphorus intake, early fortification, and vitamin D supplementation. Health care providers should closely monitor nutrient intake, postnatal growth, and screening of preterm neonates at risk for MBD. This review summarizes the critical roles of calcium and phosphorus in regulating bone physiology, how they regulate bone formation and resorption, and their influence on overall bone health.