Spandex-nylon blend fabrics (SNBF) are extensively utilized across various applications owing to their exceptional resilience and soft texture. However, inherent differences in the properties of spandex and nylon result in significant color difference after one-bath dyeing. This study aimed to enhance the dyeing efficiency and homogeneity of blended fibers by modifying the fibers and optimizing the dyeing process. Molecular structure analysis, single-factor experiments, and orthogonal experiments were employed to analyze the dyeing process and ascertain the optimal procedures. The results indicated that the optimal dyeing effect was achieved with a modifier concentration of 1% (o.w.f.), a dye concentration of 2% (o.w.f.), a pH value of 4, a dyeing temperature of 95 degrees C, and a dyeing time of 55 min. Under these conditions, the dye exhaustion (E%) reached as high as 95.4%, the homochromaticity balance value (K) was reduced from 4.74 to 1.12, and the colorimetric deviation (Delta E) was reduced by 92.2%. This process is not only suitable for one-bath dyeing of SNBF with a variety of acid dyes but also reduces temperature and time consumption, offering a novel and efficient method for one-bath dyeing of blended fibers.