The quantification of 3-nitro-l-tyrosine (NO2-Tyr), an in vivo biomarker of nitrosative stress, is indispensable for the clinical intervention of various inflammatory disorders caused by nitrosative stress. By integrating the unique features of BiVO4 and MoS2 with matching bandgap energies, electrode materials with amplified response signals can be developed. In this regard, we introduce a hydrothermally synthesized bismuth vanadate sheathed molybdenum disulfide (MoS2@BiVO4) heterojunction as a highly sensitive electrode material for the determination of NO2-Tyr. Excellent electrochemical behavior perceived for the MoS2@BiVO4 augments the performance of the sensor and allows the measurement of NO2-Tyr in biological media without any time-consuming pretreatments. The synergistic interactions between BiVO4 and MoS2 heterojunctions contribute to low resistance charge transfer (Rct = 159.13 Ω·cm2), a reduction potential Epc = -0.58 V (vs Ag/AgCl), and a good response range (0.001-526.3 μM) with a lower limit of detection (0.94 nM) toward the detection of NO2-Tyr. An improved active surface area, reduced charge recombination, and high analyte adsorption contribute to the high loading of the biomarker for improved selectivity (in the presence of 10 interfering compounds), operational stability (1000 s), and reproducibility (six various modified electrodes). The proposed sensor was successfully utilized for the real-time determination of NO2-Tyr in water, urine, and saliva samples with good recovery values (±98.94-99.98%), ascertaining the reliability of the method. It is noteworthy that the electrochemical activity remains unaffected by other redox interferons, thus leading to targeted sensing applications.