Therapeutic drug monitoring is essential for optimizing the efficacy and safety of targeted anticancer agents like imatinib, a first-line treatment for various leukemias and gastrointestinal stromal tumors. This study introduces a novel memristive biosensor designed for the detection of imatinib. The biosensor employs a silicon nanowire (SiNW) -based memristive architecture integrated with a single-stranded DNA (ssDNA) aptamer as the bio-recognition element. The detection of imatinib concentration is successfully demonstrated in both buffer and human plasma. Kinetic analysis reveals that the analysis time for achieving binding equilibrium and measurement is within 10 min. Comprehensive linear response over Imatinib concentrations in human plasma ranging from 0.2 μM to 20 μM was achieved, with a detection limit of 0.13 μM. While the interfering proteins such as human serum albumin (HSA) and α1-acid glycoprotein (AGP) compete with the binding mechanism, resulting in a decreased measured signal at lower concentrations of imatinib, their excessive presence paradoxically amplifies the measured signal. This amplification, however, also introduces increased variability in plasma measurements. This innovative memristive biosensor represents a significant advancement towards point-of-care therapeutic drug monitoring. It offers a robust and scalable platform, paving the way for the integration of personalized medicine into routine clinical workflows for imatinib-based therapies.