Herein, the fabrication and characterization of novel granisetron (GST) disposable screen-printed potentiometric sensors was described. Different fabrication protocols were introduced including; incorporation of different ions of pairing agents or GST- ion associates as electroactive sensing materials. For sake of simplicity, the dummy blank sensors can be soaked in the GST- ion associates aqueous suspension, where ion associates were extracted within the electrode matrix by the membrane plasticizer. Deep and comprehensive investigations were performed regarding the sensing matrices compositions including the influence of modifier nature and content, plasticizer, and the fabrication protocol. Incorporation of the electrode matrix with SWCNTs improved the sensor performance. Sensors modified with phosphotungstic acid showed Nernstian compliance for the GST concentration range from 10−6 to 10−2 mol L−1, adequate operational shelf lifetime (6 weeks) and fast response time (4s). Moreover, the electrode potential was pH-independent in wide range with improved selectivity. The developed sensors were introduced for GST quantification in surface water samples and pharmaceutical formulations under flow injection analysis (FIA), standard addition and potentiometric titration conditions.