In the current study, the first voltammetric method is constructed for the ultrasensitive quantification of capmatinib (CMT), a targeted therapy drug falls within the category of tyrosine kinase inhibitors (TKIs), using a modified carbon nanofibers paste electrode (CNFs-PE). Nanogold-loaded porous acetylene black (Au@PAB) as a conductive hybrid nanofiller incorporating carbon nanofiber networks (CNFs) was synthesized. The surface morphology of the synthesized Au@PAB and the ternary nanocomposite Au@PAB/CNFs was elucidated using various analytical techniques. The results show Au@PAB hybrid nanofiller incorporated CNFs has a critical property that increases electrocatalytic performance. The impact of scan rate, pH, and supporting electrolyte on the electrocatalytic response of CMT was explored on the Au@PAB/CNFs-PE nanosensor. Under optimum adsorptive stripping square-wave voltammetric (AdS-SWV) conditions, the developed probe displayed good sensitivity, selectivity, and a remarkable wide linear dynamic range of 1.0 × 10-8 – 2.0 × 10-5 M of CMT. The low limits of detection (LOD) and quantification (LOQ) were 4.6 nM and 15.4 nM of CMT, respectively. The features of easy operation and good selectivity make this nanosensor a talented candidate for CMT detection in complex samples, as demonstrated by its application in spiked biological samples with good recoveries.