Potato, a vital crop for human consumption worldwide, necessitates sustainable agricultural practices to ensure safe and high-quality tuber production. This study aimed to investigate the effects of combining mineral fertilizers with organic and biofertilizers, alongside a reduced dose of NPK (75% of the recommended rate), on the growth and yield of the potato cultivar Cara. Conducted in Isna (Upper Egypt), the experiment evaluated five fertilization treatments: Mycorrhiza + 75% NPK, EM + 75% NPK, Compost Tea + 75% NPK, 75% NPK, and 100% NPK. The results demonstrated that combining reduced doses of mineral fertilizers with organic or biofertilizers significantly enhanced potato growth and increased total yield. The produced tubers exhibited lower nitrate and nitrite levels and higher protein content. Additionally, the Mycorrhiza + 75% NPK treatment effectively reduced natural infection rates of brown rot and early blight compared to treatments using mineral fertilizers alone. This fertilization strategy presents a promising approach for implementing good agricultural practices in potato production, encouraging farmers in Upper Egypt to adopt sustainable methods to meet both local and international market demands