A novel optical refractive index sensor is proposed and theoretically investigated by cascading a PANDA and a Mach–Zehnder interferometer (MZI) based on the Vernier effect. The PANDA acts as a filter in this structure. Also, the MZI is a function of the refractive index variation. Therefore, the MZI structure acts as a refractive index sensing element in the proposed structure. Detailed modeling and instructions are provided for the design of such devices. These are supposed to be manufactured on platforms compatible with silicon-on-insulator (SOI) complementary metal-oxide semiconductor (CMOS). It is shown that the proposed sensor reaches high sensitivity (600 m/RIU) and limit of detection (LOD 3.410 RIU), which is more sensitive than the single MZI. In addition, the sensitivity of the sensor was measured when the temperature changed from 26 to 35 C. This system has many applications in the field of high-sensitivity biosensing and environmental monitoring.