The design and optimization of a surface plasmon resonance (SPR) biosensor for very sensitive detection of Mycobacterium tuberculosis are presented in this work. Using the transfer matrix method (TMM) as the primary approach, simulations using finite-element method (FEM) verified the results of the sensor. By means of materials such as the N-FK51A prism, titanium dioxide (TiO2), silicon (Si), barium titanate (BaTiO3), and black phosphorus (BP), the sensor achieves a high sensitivity of 540.67 degrees/RIU by optimizing layer thicknesses. Further performance metrics were evaluated, encompassing full-width at half-maximum (FWHM), signal-to-noise ratio (SNR), and quality factor (QF). The peak QF attained is 133.30 RIU-1, and peak SNR came to 1.031, but the lowest FWHM recorded is 3.6740 degrees, indicating precise detection capabilities. The biosensor can identify refractive index (RI) variations within the biological range of 1.29-1.35, suggesting extensive use for disease detection. A comparative analysis demonstrated that the suggested sensor surpassed current designs, particularly regarding sensitivity when utilizing BP. This study highlights the significance of material selection and layer thickness in the development of SPR biosensors for practical biological applications, enabling accurate and rapid tuberculosis (TB) detection.