Leather manufacturing is increasingly prioritizing environmentally friendly processes, emphasizing clean production to reduce environmental impacts. The present work explored the application of an α-amylase/neutral protease system (ANS) in a simplified, one-step process for unhairing, fiber opening, and bating as a viable alternative to the traditional, chemically intensive lime-sulfide system (LSS). Utilizing response surface methodology (RSM), we developed a mathematical model to optimize operational conditions, resulting in an effective concentration of 0.3 wt.% α-amylase and 0.5 wt.% neutral protease at 28.4℃ over 16.6 hours. The effectiveness of the process on unhairing and fiber opening was assessed through scanning electron microscopy (SEM), and the impact on bating was evaluated by the removal rates of carbohydrate and proteoglycan. The leather produced using the optimized ANS  exhibited physical properties comparable to those processed traditionally, with the higher hydrothermal shrinkage temperature and increased softness. Environmentally, the optimized ANS process achieved significant reductions in pollutants, cutting over 90% of chemical oxygen demand (COD), NH₃-N, and Cl^-, and reducing total solids (TS) by 73.91%. A cost analysis further revealed a direct cost savings of 30.98% when using the ANS compared to the LSS, alongside indirect savings from enhanced production efficiency and simplified wastewater treatment. Notably, the one-step enzymatic beamhouse approach substantially lowers electricity and water usage, potentially reducing greenhouse gas emissions by 44.6%. This investigation underscores the potential of ANS as a sustainable, cost-effective approach for leather manufacturing that supports environmentally friendly practices.