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Plastic waste in different environments has been constantly transforming into microplastic/nanoplastic (MNPLs). As they may coexist with other contaminants, they may behave as vectors that transport various toxic trace elements, including metals. Because the impact of exposure to such matter on health still remains elusive, the abundant presence of MNPLs has lately become a pressing environmental issue. Researchers have been utilizing Drosophila melanogaster as a dynamic in vivo model in genetic research for some time. The fly has also recently gained wider recognition in toxicology and nanogenotoxicity studies. The use of nanoparticles in numerous medical and consumer products raises serious concern, since many in vitro studies have shown their toxic potential. However, there is rather limited in vivo research into nanomaterial genotoxicity using mice or other mammalians owing to high costs and ethical concerns. In this context, Drosophila, thanks to its genetic tractability, short life span, with its entire life cycle lasting about 10 days, and distinct developmental stages, renders this organism an excellent model in testing toxic effects mediated by MNPLs. This review therefore aims to encourage research entities to employ Drosophila as a model in their nanogenotoxicity experiments focusing on impact of MNPLs at the molecular level. Drosophila as a model organism shows similar aspects around 75–77% of the genes involved in human diseases such as intestinal infections, cardiovascular diseases, neurodegenerative disorders, cancer, Alzheimer diseases, and Parkinson. The current review focuses on our current knowledge derived from recent in vivo studies to examine the impact of several MNPLs and heavy metals on Drosophila in terms of the genetic, molecular, and cellular levels; the possible mechanisms; and potential adverse effects as a non‐target organism. [ABSTRACT FROM AUTHOR]