High-risk neonates are among the most vulnerable group of population, who has greater chance and more susceptible to morbidity and mortality. So providing adequate nutritional support to high-risk neonates is a challenge. The objective of nutritional management for high-risk neonates is to provide all nutrients needed for survival and growth at all times. Nutrition Support Therapy is the provision of oral, enteral or parenteral nutrients to treat or prevent malnutrition ,meanwhile Total Parenteral Nutrition (TPN) also known as Parenteral Hyperalimenation, is an intravenous administration of all nutrients (carbohydrates, fat, vitamins, proteins, and minerals) necessary for infant’s metabolic requirements and growth. Indications of TPN are extreme premature, neonates with congenital gastrointestinal anomalies such as tracheo-esophageal fistula, omphalocele, or massive intestinal atresia. In addition to respiratory neonates with distress syndrome (RDS), infants with suspected or confirmed necrotizing enterocolitis (NEC) and expected to be NPO for more than three days and infants who are failing to gain weight on enteral feeds. Also, post-surgical infants who are unable to feed for an extended period, motility disorders as prolonged paralytic ileus following a major surgical procedure or multiple injuries, short bowel syndrome, mal-absorption syndrome, obstruction secondary to stricture or neoplasm of the esophagus or stomach. TPN is contraindicated during acute phase of any illness including; the first 2-3 days of life in babies ventilated for RDS, 3-4 days after diagnosis in babies with sepsis or NEC or if the urea or creatinine are raised as in renal failure, or any cause and in jaundice. Complications of TPN administrations including Mechanical Complications related to catheter insertion such as pneumothorax, hemothorax, laceration of vessels, air embolism, and catheter misplacement; clotting of the Catheter and Precipitation of infuscate; furthermore, specific complications such as fever and contaminated fluids. Before administering TPN, look at the solution closely and gently squeeze the bag or observe the solution container to make sure there are no leaks. Do not use the solution if it discolored or contains particles. Also, monitoring the neonates on TPN and do not change in dosing schedule. Prevention of sepsis through hand washing, aseptic technique during catheter insertion, skin cleansing at site of insertion ,using least number of hubs or lumens, keeping dressings dry, occlusive, and drainage-free, changing lines over wire using sterile technique, changing pulmonary artery catheters every five days, use central venous catheters only when necessary and finally, note accessing TPN frequently.