Introduction: Total parenteral nutrition (TPN) is essential for growth in very-low-birth-weight (VLBW) infants. The worldwide variation in TPN dosing strategies warrants investigation. This study compared clinical outcomes of aggressive, rapid-increase, and standard TPN dosing strategies in VLBW infants. Methods: A systematic review and network meta-analysis were conducted following the PRISMA NMA guideline. Searches were performed in PubMed, Scopus, Web of Science, CINAHL, CENTRAL, and ProQuest. Dosing strategies were classified as aggressive (higher starting dose), rapid-increase (standard start with rapid escalation), and standard (NICE-based). Outcomes were analyzed using a Frequentist model in RStudio v4.4.1. Results: Nine randomized controlled trials were included. Compared with aggressive and standard strategies, the rapid-increase strategy was associated with a shorter time to regain birth weight (MD = −1.43 days; 95% CI −2.82 to −0.05; P-score = 0.80). The rapid-increase strategy was also associated with a shorter length of hospitalization (MD = −0.38 days; 95% CI −6.56 to 5.80; P-score = 0.54). Regarding safety outcomes, the rapid-increase strategy had the lowest proportions of mortality (Prop = 0.043), retinopathy (Prop = 0.124), and sepsis (Prop = 0.141), but a higher proportion of patent ductus arteriosus (PDA) (Prop = 0.508). Discussion: The rapid-increase approach demonstrated the most favorable balance between efficacy and safety outcomes among the included trials, although the small number of studies is a limitation. Conclusion: Rapid-increase TPN, using the recommended starting dose but achieving maintenance more quickly, may offer clinical advantages for VLBW infants. Further long-term studies are needed to confirm developmental and metabolic impacts. 2026, Bentham Science Publishers