Marine microplastic pollution has become a global ecological and environmental issue. Under ultraviolet radiation in natural environments, microplastics gradually age, resulting in an increased surface area and an enhanced capacity to adsorb pathogenic Vibrio spp. from the water. This poses a serious threat to the survival of marine bivalves. However, the mechanism by which this combined stress affects bivalve adaptability by disrupting metabolic homeostasis remains unclear. Using the Pacific oyster (Crassostrea gigas) as a model organism, this study exposed oysters to a mixture of different concentrations of polypropylene microplastics (PPMPs) and two Vibrio spp. (Vs, Vp) for 30 days. Through an integrated analysis of histopathology, mitochondrial dynamics, and energy storage indicators, this study elucidated the mechanisms of combined exposure to microplastics and pathogenic Vibrio spp. across subcellular, tissue, and individual levels. The results showed that combined exposure to microplastics and pathogenic Vibrio spp. caused severe damage to the gill and digestive gland tissues of oysters, obstructed their energy metabolism, and reduced their feeding rate. In response to the toxic effects of combined exposure, oysters adjusted their energy allocation, which led to a reduction in gamete production, thereby potentially compromising population reproduction. This study provides new insights into the practical toxic effects arising from the combined pollution of microplastics and Vibrio spp.