Mercury is one of the top three most hazardous substances (Agency for Toxic Substances and Disease Registry). It is among one of the highly toxic water pollutants causing damage to the brain, lungs, nervous system, and many other vital human organs. Hence, detecting Hg(II) at the lowest concentration (picomolar-femtomolar) is highly desirable to avoid adverse health effects. This article outlines an insightful electrochemical sensor platform for ultraselective sensing of Hg(II) with Self Assembled Monolayers (SAM) of mercaptosuccinic acid (MSA) cross-linked pyridinedicarboxylic acid (PDCA) on top of indium doped ZnO nanofibers (InZnO-NF). The sensor achieves a limit of detection (LOD) 3.13 fM. To improve charge transport properties, indium-doping is used. The MSA-PDCA combination with multifunctional strategy has excellent selectivity towards targeted Hg(II) ions because of its highest stability constant and strong coordinate covalent bond of carboxyl groups (–COOH) with Hg(II). The interaction of Hg(II) ions with InZnO/MSA-PDCA is observed in terms of a change of charge transfer resistance (Rct), which is used as a primary sensing parameter and directly proportional to the mass of targeted Hg(II) ions. The proposed portable electrochemical sensor is the first of its kind capable of ultrasensitive detection of Hg(II) ions in the femtomolar range and useful as a Point-of-care testing platform. © 2022