<p>This study looked at the aldol condensation process from a theoretical point of view using the high-performance single-atom catalysts Co/Al₂O₃, Cu/Al₂O₃, and Ni/Al₂O₃. Density functional theory (DFT) computations elucidated the structures, intermediates, and products of this process, conducted using the M06-2X technique and the SVP basis set. This work included the construction and examination of single-atom catalysts by individually depositing nickel, copper, and cobalt metals onto the surface of gamma alumina (<i>γ</i>-alumina). The DFT findings indicate that spin states 2, 3, and 4 represent the most stable configurations for copper, nickel, and cobalt, respectively. Polar solvents, including water, ethanol, and acetone, were used for solvent calculations, which ultimately indicated that the gas phase is much more advantageous for this reaction. Furthermore, it is noticeable that the cobalt catalyst (with overall barrier = 11.0&#xa0;kcal/mol) demonstrates the highest efficiency within the gas phase of the mechanism. NBO calculations provide a clear depiction of electron resonance along the reaction pathway. The findings of this study will enhance comprehension of the response mechanism in experimental investigations. This finding may serve as a precursor to more research in single-atom catalysts.</p>