This work investigates the influence of various 2D (two-dimensional) materials and transition metal dichalcogenides (TMDC) on a bimetallic multilayered plasmonic sensor. Using numerical modeling and simulation with Au and Ag over a prism BK7 in Kretschmann configuration, the sensor is optimized through the transfer matrix approach and angle interrogation method. Each 2D and TMDC nanomaterial is individually analyzed on the bimetal. Findings reveal that black phosphorus (BP) achieves the highest sensitivity at 360°/RIU, with other materials showing sensitivities between 120 and 180°/RIU. Sensing performance parameters like the figure of merit (FoM), limit of detection (LoD), detection accuracy (DA), and Q-factor are 189.47 RIU-1, 1.38×10-5, 0.175 degree-1, and 0.947 respectively. The sensor’s efficacy for glucose detection in urine samples shows a sensitivity of 294.4°/RIU, LoD of 1.6×10-5, detection accuracy of 0.3745 degree-1, FoM of 110.2 RIU-1, and Q-factor of 0.1498. The comparative analysis demonstrates substantial advancements in the 1.330–1.335 refractive index range and for urine glucose detection, emphasizing the sensor’s potential in biological sensing and biomedicine.