In recent years, metallic nanostructures have become essential in biosensing due to their unique optical properties, making them excellent optical transducers. Among various fabrication techniques, solid-state dewetting of nanofilms provides a fast and cost-effective method for creating large-scale plasmonic arrays. However, the interaction between the supporting substrate and the metal nanostructure plays a critical role in the localized surface plasmon resonance (LSPR) sensitivity, influencing the local refractive index (RI) of the nanostructure. In this study, we demonstrate the development of hybrid Au–Si 3 N 4 nanostructures that exhibit enhanced localized surface plasmon resonance (LSPR) sensitivity and an exceptionally low detection limit (LOD) for streptavidin in the subfemtomolar range. To achieve even greater performance, the Si 3 N 4 substrate undergoes an etching process, which further refines the features of the nanostructures, leading to improved sensing capabilities. This enhancement, achieved through substrate etching, plays a crucial role in maximizing the sensitivity and effectiveness of hybrid nanostructures for advanced biosensing applications. The large-scale fabrication process of hybrid nanostructures enables remarkable performance in refractive index (RI) sensitivity. Indeed, the obtained nanostructures display a high average RI sensitivity, making them highly effective for biomedical sensing applications where detecting changes in RI is crucial. The results of this work demonstrate that combining hybrid plasmonic and dielectric materials can significantly enhance sensing performance and, when integrated into silicon-based optoelectronic devices, expand their use in advanced biosensing technologies.