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Surface Plasmon Resonance (SPR) sensors are a useful tool for biomolecule detection, offering label-free and real-time monitoring characteristics. However, traditional SPR sensors still face the challenges of limited detection sensitivity, especially for sensing small molecules with a low concentration level (less than 1 pM (10−12 mol/L)). To overcome this challenge, in this paper, we designed a Kretschmann configuration which uses a plasmonic waveguide to generate a powerful Fano resonance through the coupling of the surface plasmon polariton (SPP) mode and photonic waveguide (PWG) mode at the sensing interface. By optimizing the thickness of the layers of the metamaterial structure, it is also possible to adjust the resonance angle, the reflectivity, the quality factor (Q factor), the intensity sensitivity, the angular sensitivity and the detection range. In our designed subwavelength grating waveguides (SWG) structure sensor, the intensity sensitivity reached 1.808 × 104 RIU−1, which surpassed the intensity sensitivity of uniform Si layers by 5.14 times. This approach provides a framework for physicists and biologists to develop the future generation of medical diagnostic devices. [ABSTRACT FROM AUTHOR]