<p>Titanium oxide nanoparticles (TiO₂-NPs) have extensive industrial applications as pharmaceuticals, cosmetics, sunscreens, implanted biomaterials, paints, printing ink, etc. However, extensive industrial usage leaves a trail of toxicological implications on the ecological cascade through biological uptake and accumulation. Being the major sink, the aquatic environments might often get adversely affected at different levels of biological organization – from genetic to systemic levels depending on nanoparticles’ size, surface area, agglomeration, surface properties and exposure window. Upon exposure, the TiO₂-NPs have been shown to cause oxidative stress, genotoxicity, and histopathological alterations. TiO₂-NPs can bind with free radicals and signal molecules and interfere with several biochemical reactions in the plasmalemma. All these toxicological challenges draw attention of the researchers to focus more on the not-so-explored territory of the nanoparticle’s toxicity and associated changes, which could provide an insight into their environmental relevance and ecotoxicological risk. This study is the only one integrating current data on TiO₂-NPs interactions across several trophic levels and environmental compartments. It emphasises on the consequences on non-target aquatic animals under actual exposure situations.</p> Graphical Abstract <p></p>