Emerging zoonoses pose significant public health risks and necessitate rapid and effective treatment responses. This study enhances the technology for preparing Molecularly Imprinted Polymers (MIPs), which function as synthetic nanoparticles targeting SARS-CoV-2 receptor-binding domain (RBD), specifically the Omicron variant, thereby inhibiting its function. This study builds on previous findings by introducing precise adjustments in the formulation and process conditions to enhance particle stability and ensure better control over size and distribution, thereby overcoming the issues identified in earlier research. Following docking studies, imprinted nanoparticles were synthesized via inverse microemulsion polymerization and characterized in terms of size, morphology and surface charge. The selective recognition properties and ability of MIPs to obstruct the interaction between ACE2 and the RBD of SARS-CoV-2 were assessed in vitro, using Non-Imprinted Polymers (NIPs) as controls, and rebinding studies were conducted utilizing a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D). The synthesized nanoparticles exhibited uniform dispersion and had a consistent diameter within the nanoscale range. MIPs demonstrated significant recognition properties and exhibited a concentrationdependent ability to reduce RBD binding to ACE2 without cytotoxic or sensitizing effects. MIPs-based platforms offer a promising alternative to natural antibodies for treating SARS-CoV-2 infections, therefore representing a versatile platform for managing emerging zoonoses.