Silica is a commercially significant material due to its extensive use in widespread applications and products. Synthetic amorphous silica (SAS) is a form of SiO₂ that is intentionally manufactured and has been produced and marketed for decades without significant changes in its physico-chemical properties. The industrial production of nanostructured SiO₂ is nowadays challenged by the expensive raw material use and high energy consumption. The search for non-petroleum-based fillers such as nanostructured SiO₂, which are environmentally friendly, cheap, abundant, renewable, and efficient, has been initiated nowadays. Therefore, a large number of research activities have been carried out so far for the preparation of SAS from potential alternate precursors, i.e., synthetic chemicals, biogenic, and mineral ore resources. Reinforcement of rubbers with nanostructured SiO₂ fillers is a process of great practical and technological importance for improving their mechanical, dynamic, and thermal properties. The efficiencies of SiO₂ reinforcement correlate with different factors such as filler structure, surface area, rubber–filler interactions, and filler–filler interactions with their effects. This review paper discusses the recent synthesis advances of nanostructured SiO₂ from synthetic chemicals, biogenic and mineral ore resources, their physical characteristics, and applications in rubber reinforcement, overcoming challenges. Finally, summary and future work recommendations have been mentioned well for future researchers.