Photocatalysts exhibiting high activity for the degradation of 1,4-dioxane (1,4-D) have been a subject of intense focus due to their high toxicity and challenging degradability. Bismuth oxide (Bi2O3) is recognized as an ideal photocatalyst; however, there have been limited studies on its effectiveness in 1,4-D degradation. It is crucial to address the issue of low photocatalytic efficiency attributed to the instability and easy recombination of photogenerated electrons and holes in Bi2O3 upon photoexcitation. In this study, Cu-MOF and oxygen vacancy were utilized to improve the 1,4-D photocatalytic degradation efficiency of Bi2O3 by preparing Bi2O3, Bi2O3/Cu-MOF, Bi2O3−x, and Bi2O3−x/Cu-MOF. The results revealed that the incorporation of Cu-MOF induced a larger specific surface area, a well-developed pore structure, and a smaller particle size in Bi2O3, facilitating enhanced visible light utilization and an improved photoelectron transfer rate, leading to the highest photocatalytic activity observed in Bi2O3/Cu-MOF. In addition, oxygen vacancies were found to negatively affect the photocatalytic activity of Bi2O3, mainly due to the transformation of the β-Bi2O3 crystalline phase into α-Bi2O3 caused by oxygen vacancies. Further, the synergistic effect of MOF and oxygen vacancies did not positively affect the photocatalytic activity of Bi2O3. Therefore, the construction of heterojunctions using Cu-MOF can significantly enhance the efficiency of degradation of 1,4-D, and Bi2O3/Cu-MOF appears to be a promising photocatalyst for 1,4-D degradation. This study opens new avenues for the design and optimization of advanced photocatalytic materials with improved efficiency for the treatment of recalcitrant organic pollutants.