The Surface Plasmon Resonance (SPR) Sensor is an efficient and effective method with a label-free, highly sensitive, and quick detection mechanism to identify modifications in the refractive index (RI) of the surrounding environment. In this work, MPS-modified ceria or cerium oxide is used for target analyte binding due to its high sensitivity towards the RI shift. The suggested SPR sensor accomplishes a sensitivity of 295.27 RIU−1, which is better than the state-of-the-art conventional SPR (C-SPR) sensor. Similarly, the detection accuracy of 0.3584 and a higher FOM of 43.02 is achieved which makes the sensor most suitable for biomolecule detection. The chemically stable and corrosion-resistive nature of gold makes the sensor suitable and stable for inspection of biomolecule applications and so on. Sensor design optimization and performance analysis of the suggested structure are performed using MATLAB software. The novel proposed ceria-mediated SPR sensor design can be suitably used for biomolecule sensing.