The high morbidity, mortality, and huge numbers of affected individuals have delineated cardiovascular diseases as one of the most vulnerable global health burdens. Amongst the top proteins to reflect ventricular dysfunction, Brain-type natriuretic peptide (BNP or ProBNP) carries substantial potential towards estimating human heart risk, both at the prognostic and diagnostic level. Herein, clinically significant concentrations of ProBNP ranging from 100 fg/mL to 100 ng/mL are assessed via a hydrothermally synthesized 2-D SnS2 nanomaterial enhanced ultrasensitive and selective portable electrochemical biosensor. X-ray Diffraction, Scanning Electron Microscopy, Transmission Electron Microscopy, and Fourier Transform Infra-Red Spectroscopy are performed for material characterization. The transduction mechanism is realized through the covalent immobilization of the target-specific antibodies on the bioelectrode surface. Multiplex trigger signals, i.e., cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), are employed to explore the antigen-antibody binding event. The sensitivity of the proposed sensor is found to be 11.7355 (ΔR/R) (ng/mL)−1cm−2 in case of EIS and 103.2396 (ΔIp/Ip) % (ng/mL)−1cm−2 in case of DPV with the lowest limit of detection being 0.225 fg/mL (SNR=3.3) for 5 mg/mL SnS2-DMF dispersion. Further, it is subjected to interference, stability, selectivity, and recovery studies in PBS and plasma matrix aiming at the on-field diagnostic performance. © 2022