Pearl farming is crucial for the economy of French Polynesia. Nonetheless, rearing structures contribute significantly to plastic waste, and the widespread contamination of pearl farming lagoons by microplastics has raised concerns about risks to the pearl industry. This study aimed to evaluate the effects of micro-nanoplastics (MNPs) on the pearl oyster (Pinctada margaritifera) over a 5-month pearl production cycle by closely mimicking ecological scenarios. MNPs were produced from plastic pearl farming gear and tested at environmentally relevant concentrations (0.025 and 1 µg L–1 ) to decipher biological and functional responses through integrative approaches. MNP exposure altered energy metabolism, primarily driven by lower assimilation efficiency of microalgae, causing shifts in gene expression patterns. A gene expression module was strongly correlated with physiological parameters impaired by MNP conditions, and key genes were identified as potential environmental proxies to assess nutritional-MNP stress conditions in cultured oysters. Pearl biomineralization was also affected, resulting in thinner aragonite crystals, and harvests were marked by abnormal biomineral concretions, known as keshi pearls. Ecological approaches are now necessary to assess the overall impact of MNPs on population maintenance and sustainability within the Polynesian pearl industry, considering the context of the exposome and global climate change.