Imatinib is the standard first line treatment for chronic myeloid leukemia (CML). Owing to doserelated toxicities of Imatinib such as neutropenia, there is scope for treatment optimization through therapeutic drug monitoring (TDM). Trough concentration of 1 μg/mL is considered the therapeutic threshhold. Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation. Hence, Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration. Three approaches: conventional Raman spectroscopy (CRS), Drop coating deposition Raman (DCDR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) were employed to detect the required trough concentration of 1 μg/ mL and above. Detection of therapeutically relevant concentrations (1 μg/mL) using SERS and suitable nanoparticle substrates has been demonstrated. Prospectively, rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.