Janus nanoparticles (JNPs) represent a singular group of functional materials that exhibit an asymmetrical structure, namely two hemispheres of different chemical compositions. Currently, several raw materials are employed to develop Janus nanoparticles. Among them, silica nanoparticles exhibit significant advantages over other starting materials due to their relatively simple synthesis and modification, high porosity, excellent adsorption capacity, extraordinary colloidal stability, and biocompatibility. Therefore, this review aims to offer a systematic assessment of silica-based Janus nanoparticles, providing a clear description and illustration of the available synthesis methods, which for clarity have been classified into three main categories: masking, self-assembly, and phase separation. The review also discusses the most convenient paths for determining the amphiphilic character of these particles due to the relevance of this property, as well as their potential application in three main areas, including medicine, environment, and energy. Additionally, the reader can find an account of the SiO2-based JNPs shapes reported in the literature, which are summed up in tables to facilitate the identification of their properties and proved applications. The last section is dedicated to discussing the prospects for the synthesis methods of JNPs, the behavioral prediction, and approaches for their characterization and further application.