Pearl farming is the second most important economic resources of French Polynesia. However, rearing structures are an important source of plastic waste and the widespread contamination of pearl farming lagoons by microplastics has led to questions about risks for the pearl industry. The aim of this study was to test the effects of micro-nanoplastics (MNPs) on the pearl oyster (Pinctada margaritifera) over a 5-month pearl production cycle by closely mimics environmental scenarios. MNPs were produced from plastic pearl farming gear and used at concentrations (0.025 and 1 µg L–1) that oysters may encounter in lagoons to decipher biological and functional responses using integrative approaches. MNP exposure led to the alteration of energy metabolism, mostly driven by a lower assimilation efficiency of microalgae, with modulation of gene expression patterns. A module gene expression was strongly correlated with physiological parameters impaired by MNP conditions. Expression of key genes was suggested to be highly conserved in pearl oyster tissues (mantle, hemocytes and pearl sac) and may be used as potential environmental proxies to assess nutritional-MNP stress conditions of cultured oysters. Pearl biomineralization was also impacted by thinner aragonite crystals, with harvest marked by the presence of abnormal biomineral concretions, called keshi pearls. These experimental results demonstrated that MNPs threaten oyster physiology, with potential detrimental effects on pearl quality. Ecological approaches are now required to test the holistic impact of MNPs on population maintenance and sustainability in the Polynesian pearl industry in the context of the exposome and global climate change.