Vancomycin is a cornerstone agent in the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other penicillin-resistant gram-positive bacteria. Due to its narrow therapeutic window and substantial interindividual pharmacokinetic variability, individualized dosing is crucial. Therapeutic drug monitoring (TDM) enables dose adjustments based on patient-specific pharmacokinetic parameters and measured serum concentrations, thereby enhancing therapeutic efficacy while minimizing adverse effects, such as nephrotoxicity. Variations in renal function, underlying comorbidities, and concomitant use of nephrotoxic medications are important clinical determinants that increase the need for TDM. Additionally, careful monitoring is required due to infusion-related reactions, acute kidney injury, and hematologic toxicities associated with vancomycin therapy. Current guidelines recommend shifting from trough concentration–based monitoring to evaluation of the 24-hour area under the concentration–time curve/minimum inhibitory concentration (AUC24/MIC) ratio, particularly in the management of severe MRSA infections. However, because many centers lack the infrastructure required for routine AUC-based monitoring, trough-based TDM remains widely used and clinically relevant. In this narrative review, we synthesize current guideline recommendations and established reference sources in infectious diseases and clinical pharmacology to provide a comprehensive overview of the scientific principles, practical methods, target pharmacokinetic/pharmacodynamic thresholds, and real-world challenges associated with vancomycin TDM in adult patients. This work aims to support the standardization of TDM practices and to contribute to improving the safety and effectiveness of vancomycin use in clinical settings within our country.