This study presents a numerical study of a highly sensitive photonic crystal fiber (PCF) surface plasmon resonance (SPR) sensor capable of detecting five types of cancer and bacterial contamination in water. By precisely arranging only two air holes in a single channel of an elliptical-shaped PCF, the sensor maximizes interaction between core-guided modes and surface plasmon polaritons (SPP) along the fiber. Evaluation using COMSOL Multiphysics simulation software, based on finite element method (FEM), demonstrates outstanding sensor performance across a wide refractive index (RI) range (1.33 to 1.43). With a maximum wavelength sensitivity (WS) of 188,000 nm/RIU and amplitude sensitivity (AS) of -22,377.99 RIU−1, the sensor achieveStructural Design and Methodologys a sensor resolution (SR) of 5.3191 × 10−7 RIU and figure of merit (FOM) of 854.55 RIU−1. Notably, it exhibits AS and WS values tailored for specific cancer cell types and water contamination. These results endorse the sensor’s potential in diverse biological and molecular analyte RI detection applications within the visible to near-infrared (VNIR) range (0.55 to 4 µm), offering high sensitivity, affordability, wide sensing range, good linearity, low propagation loss, and simplicity in construction.