Therapeutic drug monitoring (TDM) is a valuable clinical tool in optimisation of drug regimens. However, improper utilisation of TDM may lead to significant resource wastage and expose patients to avoidable trauma, toxicity, therapeutic failure and prolonged hospitalisation. This study aimed to reduce the percentage of inappropriate TDM sampling to our proposed standard of less than 20% within a four-month intervention period. A cross-sectional study was undertaken from January to December 2015 at the inpatient setting of Hospital Sultanah Nur Zahirah. Gentamicin and Vancomycin analytes were studied because these analytes accounted for 69.2% of total samples received in 2014. TDM Monitoring Form was used to collect sampling and dosage information to assess sampling appropriateness. A closed-ended self-administered questionnaire was distributed to a group of medical doctors to assess their knowledge on appropriate Gentamicin and Vancomycin TDM sampling method pre- and post-intervention. Prior to the intervention phase in October to December 2014, 79.4% of TDM were inappropriately sampled. The main contributing factors were inadequate knowledge among medical doctors, lack of sampling reminders for new TDM requests, and misunderstanding on sampling information for repeated TDM requests. 60-minute face-to-face educational sessions on TDM sampling method were conducted specifically for staff at the General Medical and Paediatric Departments, and two continuing medical education (CME) slots were held at the hospital level. Guidelines on TDM sampling was initiated and laminated copies were distributed to all wards. Implementation of TDM Alert System which consisted of digital reminders and physical stickers was also introduced. The interventions were able to reduce the inappropriate sampling percentage from 79.4% to 41.8% post-intervention, and to 19.1% in the recent monitoring phase of January until June 2019. Continuous close monitoring and sustainable implementation of the measures are vital as TDM sampling appropriateness may affect clinical interpretation of the results.