We propose a strategy to improve sensing performance of sub-wavelength-grating (SWG) waveguide-based sensors by introducing a substrate-overetch (SOE) geometry. The proposed SOE-SWG waveguide shows enhanced analyte interaction and a reduced group index, which improves the sensitivity of resonator-based sensors. The SiO2 overetch process was realized in Ar/C4F8/O2 plasma for 40 sec with a SiO2/Si selectivity of 10:1, obtaining a 285-nm anisotropic overetch in the SiO2 layer. Sensor performance of the SOE-SWG architecture is characterized by using isopropyl alcohol solutions, indicating an enhanced bulk sensitivity up to 575 nm/RIU (479 nm/RIU before the SOE), and a maximum waveguide mode sensitivity larger than one.