In this work, we introduce a new perspective on the development of Localized Surface Plasmon Resonance (LSPR) optical biosensors. Computational simulations, focused on the assessment of the LSPR spectrum and spatial distribution of the electromagnetic field enhancement near a metallic nanoparticle, elucidated the behavior of crucial parameters, as figure of merit, bulk and molecular sensitivity, which governs a LSPR sensor performance. Gold and silver nanospheres were explored as starting point to assess plasmonic optical characteristics of the nanostructured sensor platform. Here, for the first time in the literature, Campbell's model was evaluated exploiting a NP size-dependence approach. The theoretical analyses indicate a nonlinear behavior of the bulk and molecular sensitivity as function of the NP size. Substantial LSPR peak shifts due to the adsorption of molecules layer on a NP surface were observed for nanoparticles with ~5 nm and ~40 nm radius. Moreover, on molecular sensing, LSPR peak shift is also determined by the thickness of adsorbed molecular shell layers. We observed that for 40 nm radius gold and silver nanospheres, significant LSPR peak shift could be induced by small (few nm) thickness change of the adsorbate shell layer. Moreover, this work provides insights on the LSPR behavior due to adsorption of molecular layer on a NP surface, establishing a new paradigm on engineering LSPR biosensor. Furthermore, the proposed approach can be extended to engineer an efficiently use of different nanostructures on molecular sensing.