The COVID-19 pandemic has further intensified plastic pollution due to the escalated use of single-use gloves and masks, consequently leading to the widespread presence of microplastics (MPs) and nanoplastics (NPs) in major rivers and lakes worldwide. Macrobrachium rosenbergii has become an important experimental subject due to its ecological role and environmental sensitivity. In this study, we sought to comprehend the ramifications of NPs on the widely-distributed freshwater prawn, M rosenbergii, by conducting a detailed analysis of its responses to NPs after both 96 h and 30 days of exposure. The transcriptome analysis revealed 918 differentially expressed unigenes (DEGs) after 30 days of NPs exposure (356 upregulated, 562 downregulated) and 2376 DEGs after 96 h of NPs exposure (1541 upregulated, 835 downregulated). The results of DEGs expression indicated that acute NPs exposure enhanced carbohydrate transport and metabolism, fostering chitin and extracellular matrix processes. In contrast, chronic NPs exposure induced nucleolar stress in M. rosenbergii, impeding ribosome development and mRNA maturation while showing no significant changes in glucose metabolism. Our findings underscore the M. rosenbergii distinct coping mechanisms during acute and chronic NPs exposure, elucidating its vital adaptive strategies. These results contribute to our understanding of the ecological implications of NPs pollution and its impact on aquatic animals.