The mortality of people worldwide caused by COVID-19 has enhanced the research interest to design and develop power-efficient, low-cost, and sensitive biosensors to detect a wide range of biomolecules or foreign particles that can cause severe negative impact on humans. A novel Bio-RFET biosensor with hetero-material (HM) for source/channel and drain regions and hetero-dielectric (HD) is proposed, which acts as an n -MOSFET or a p -MOSFET and n -TFET or p -TFET. This HM-HD-RFET biosensor senses the biomolecules by the label-free dielectric modulation (DM) technique. When the biomolecules are present in the nanocavity, the biosensor can detect the biomolecules without labeling costs. It also changes the dielectric polarization within the nanocavities, and causes a drain current variation in the presence of an electric field. In this research article, (SiO 2 + TiO 2 ) and an AlGaAs/Ge-based HD-HM-RFET have been analyzed for their use in biosensing. We found that the proposed device exhibits higher sensitivity as compared to a SiO 2 + HfO 2 -HM-RFET and a Si-based SiO 2 + TiO 2 -RFET for varying dielectric constants ( K ) from K = 20-80 and charge densities in the range - 5 × 10 11 to 1 × 10 13 C/cm 2 . Further, it can be noticed that n -SiO 2 + TiO 2 -HM-TFET possesses the highest I d -V gs sensitivity of 5.09 × 10 13 , I ON /I OFF ratio of 1.23 × 10 9 , lowest SS of 20.3 mV/dec, and V th of 1.48 V.