This study explores the valorization of waste potatoes for bioethanol production through optimized saccharification and fermentation processes. A bifactorial experiment (P < 0.05) using Response Surface Methodology (RSM) assessed the influence of steam pretreatment, enzyme concentration, substrate levels, inoculum density, and microbial strains on ethanol yield, yeast growth, and glucose conversion efficiency. Fermentation time emerged as the most significant factor (P < 0.01), followed by substrate concentration. Under optimal conditions, the maximum ethanol yield (9.1% w/v) and glucose conversion efficiency (91%) were achieved. Saccharification efficiency (96%) was primarily influenced by temperature (65 °C), enzyme cocktail composition (α-amylase 265 U, amyloglucosidase 115 U, pullulanase 167 U), reaction time (11.5 h), and pH (6.4). The optimal fermentation conditions included an inoculum concentration of Saccharomyces cerevisiae MTCC 178 at 4.24%, a fermentation duration of 85 h, and a fermentable sugar concentration of 23%. The experimental results closely matched predicted values, confirming model robustness. This research highlights the potential of waste potatoes as a sustainable feedstock for bioethanol production, offering economic and environmental benefits. Future studies should focus on enzyme kinetics and process scale-up to enhance industrial bioethanol yields.