Abstract: Catalysis remains a pivotal area of study within the chemical sciences, representing a cost-effective, energy-conserving, and eco-friendly approach for facilitating energy transformations and synthesizing value-added chemical products. The quest for an efficient and robust catalyst is motivated by advancing various industries and addressing global challenges, single-atom catalysts (SACs), with 100% atomic utilization and unique electronic structure, have attracted considerable attention from the domestic and foreign research institutions. However, the instability and thermal sintering of SACs remains a challenge, which leads to deactivation over time. The key to the commercial application of SACs lies in their large-scale synthesis and application in important industrial reactions. In this review, the research progress on scalable synthesis method of SACs, including high-temperature fusing and precursor-atomization strategies, was provided. The single Fe sites confined within SiO₂ (0.5%Fe©SiO₂) only dissociate the first C−H bond of methane, effectively avoiding the deep dehydrogenation of methane and eliminating coke formation during direct, nonoxidative conversion of methane towards olefins, aromatics, and hydrogen. Flame spray pyrolysis (FSP) stands out as a simple, versatile, and scalable synthetic strategy for the synthesis of SACs at kilogram scale per hour, enabling the precise control of metal dispersion and support interaction. The FSP process is highly sensitive to various parameters, including the flow rate of the carrier gas, the concentration of the precursor solution, the temperature of the flame, and the residence time of the precursor in the flame. Optimizing these parameters is essential for achieving the desired size, morphology, and dispersion of the resulting SACs. Therefore, we focus on the FSP synthesis parameters, support materials, metal precursors, and catalytic property in various reactions, reviewing the advancements in SACs fabrication via FSP. Mo-, Pt-, Pd-, La-, Zr-based SACs were prepared via FSP method, and employed in direct nonoxidative conversion of methane, CO oxidation, CO₂ hydrogenation to methanol, and photocatalytic reactions, showing excellent catalytic performances. Compared with the traditional wet synthetic method, the SACs prepared by FSP have the advantages of excellent high-temperature structural stability, anti-coking, and controllable phase and spatial distribution of multicomponent. The result shows methyl radical chemistry could be a general characteristic for SACs during the direct nonoxidative conversion of methane. On the other hand, it is demonstrated that the particle size of FSP-synthesized CeO₂ support influences the activity of Pd-based SACs in CO oxidation reaction, which is indicative for the support size-dependent redox properties of Pd-based SACs. A perspective for FSP-made SACs was forecasted. Flame spray pyrolysis technology has shown great potential in the bench fabrication of SACs with high loading and sintering resistance. The understanding of general principle and formation mechanism for FSP-made SACs will be deepened using operando spectroscopy and microscopy techniques, paving the way for the rational design of more active, selective and stable catalysts. The FSP method for non-precious metal (such as Fe, Co, Ni, Cu, Zn) based SACs will be developed and their potential applications in heterogeneous catalytic reaction will be explored. Looking forward, the integration of machine learning and high-throughput screening with FSP could accelerate the discovery of new SACs and optimize the synthesis parameters.