Alpha-ketoglutaric acid (α-KGA) possesses significant therapeutic potential in oncology and post-operative care. However, its application is limited by poor cellular membrane permeability. The main aim of this study was to overcome this limitation,enhancing the number of α-KGA getting through. For this reason, the dimethyl-αketoglutarate (DM- α-KG) was synthesized. This molecule can be utilized due to its substantially enhanced cellular uptake, particularly in malignant cancer cells. Considering the therapeutic importance of DM-α-KG, Fischer esterification of α-KGA was carried out to synthesize dimethyl-α-ketoglutarate (DM-α-KG) using paratoluenesulfonic acid monohydrate (p-TsOH·H₂O) as a homogeneous catalyst. Comprehensive experimental investigations were performed by varying key reaction parameters, including temperature, reagent concentrations, catalyst type and loading, and reaction composition, particularly the amounts of methanol and methyl isobutyl ketone, to maximize the yield of DM-α-KG. Furthermore, a kinetic study was conducted to establish fundamental parameters for potential large-scale industrial applications. In addition, the recyclability of the catalyst was evaluated over consecutive reaction cycles, highlighting its importance for process sustainability and economic feasibility.