Abstract: To improve the quality of Shaanxi tobacco leaves, the enzyme production conditions of the extracellular enzyme system from Bacillus velezensis NDX-93 were synergistically optimized to enhance its capability to degrade macromolecular substances in tobacco leaves. Single-factor and orthogonal experiments were conducted to optimize the enzyme production conditions, and the effects of the extracellular enzyme system on the chemical components, volatile compounds, and sensory quality of tobacco leaves before and after optimization were analyzed. The results showed that the optimal enzyme production conditions were as follows: fermentation time of 36 h, temperature of 35 °C, initial pH of 7.0, and shaking speed of 180 r/min. Compared with those before optimization, the degradation rates of protein, starch, cellulose, and pectin in tobacco leaves by the optimized enzyme solution increased by 34.69, 27.54, 16.07, and 12.34 percentage points, respectively. The increased enzyme activity significantly influenced the changes in various volatile substances, including methyl butyrate, damascenone, theaspirone, and methyl nonanoate. Methyl butyrate, 6-methyl-2-heptanone, and methyl (3Z)-3-hexenoate were significantly positively correlated with improvements in aroma quality, aroma abundance, softness and fineness, and the reduction of off-odor. Through synergistic optimization of the enzyme production conditions, the activity of the NDX-93 enzyme system was significantly enhanced, the degradation efficiency of the optimized enzyme solution for tobacco leaf macromolecules was improved, aroma substances were enriched, and tobacco leaf quality was significantly improved.