Early differentiation of healthy and cancerous skin tissue models requires sensitive optical platforms capable of detecting subtle refractive index variations in biological media. In this study, a multilayer Surface Plasmon Resonance (SPR) sensor in the Kretschmann configuration with a BK7/Ag/ZnO/TiO₂/BP architecture was numerically designed and optimized using the Transfer Matrix Method (TMM) at a wavelength of 633 nm. The primary objective was to simultaneously leverage the optical properties of black phosphorus (BP) and the dielectric properties of TiO₂ and ZnO layers to enhance the interaction of the electromagnetic field with the sensing medium and improve the plasmonic response to refractive index changes. During the optimization process, the thickness of the silver layer, the thicknesses of the dielectric layers, and the number of BP layers were systematically investigated. The results demonstrated that the optimized structure—comprising a 52 nm silver layer, 4 nm ZnO and 2 nm TiO₂ layers, and three BP layers—offered the highest performance among the evaluated configurations. This structure is capable of detecting the refractive index shift from 1.36 in the healthy tissue model to 1.38 in the cancerous tissue model, exhibiting an angular sensitivity of 354 deg/RIU and a Figure of Merit (FoM) of 83.87 RIU⁻¹. The findings indicate that combining ZnO, TiO₂, and BP layers can improve sensor performance against refractive index variations by modifying plasmonic coupling conditions and increasing electromagnetic field interaction with the sensing environment. Consequently, the proposed architecture holds promise as a suitable optical platform for refractive-index-based discrimination between healthy and cancerous skin tissue models. However, since the present study is based on numerical refractive index modeling, confirming its capability for selective detection of specific cancer cells or biomarkers will require experimental validation and the integration of specific bioreceptors in future studies.