Introduction: Vancomycin is commonly administered to neonates, while observational data on therapeutic drug monitoring (TDM, trough levels) suggest that vancomycin exposure and dosage remain substandard.Area covered: Data on vancomycin pharmacokinetics (PK) and its covariates are abundant. Consequently, modeling is an obvious tool to improve targeted exposure, with a shift from TDM trough levels to area under the curve (AUC24h) targets, as in adults. Continuous administration appeared as a practice to facilitate AUC24h target attainment, while Bayesian model-supported targeting emerged as a novel tool. However, the AUC24h/MIC (minimal inhibitory concentration) target itself should consider neonate-specific aspects (bloodstream infections, coagulase-negative staphylococci, protein binding, underexplored causes of variability, like assays, preparation and administration inaccuracies, or missing covariates).Expert opinion: To improve targeted exposure in neonates, initial vancomycin prescription should be based on ‘a priori model-based individual dosing’ using validated dosing regimens, followed by further tailoring by dosing optimization applying Bayesian estimation-assisted TDM. Future research should focus on the feasibility to integrate these tools (individualized dosing, Bayesian models) in clinical practice, and to perform PK/PD studies in the relevant animal models and human neonatal setting (coagulase-negative staphylococci, bloodstream infections).