The fate and behavior of nano-sized materials in aquatic ecosystems, as well as their interactions with other organic and inorganic pollutants, remain largely unexplored, presenting a real challenge. Data regarding the combined effects of nanoparticles (NPs) and various pollutants on aquatic organisms, food chains, and ecosystem sustainability are notably scarce. NPs exhibit unique physicochemical properties that render them useful in fields such as biomedicine, industry, and environmental protection. Within the European Union, efforts to tighten controls on hazardous pollutants and increased environmental requirements for preserving a sustainable environment and human health continuously stimulate the search for innovative wastewater treatment technologies. Certain NPs have robust sorption capacities, making them viable candidates for removing pollutants from aquatic environments. However, once introduced to the environment, NPs may accumulate in aquatic ecosystem, potentially leading to unpredictable changes in the functional status of organisms. A full comprehension of the impact mechanisms of NPs interactions with other pollutants requires additional research to elucidate how the physicochemical properties of NPs are related to their effects on living organisms. In this investigation, we aim to explore the effects of carbon-, metal-, and polymer-based NPs, as well as their mixtures with metals and pharmaceuticals, on fish and crustaceans. Our methodology will not only employ conventional ecotoxicological techniques but also take advantage of an innovative system breeding and rearing (Tecniplast), evaluating morphophysiological parameters (Danioscope and Daniovision), and utilizing analysis systems (Embryonet, MetaboAnalyst) for Danios rerio and other small aquatic organism. This study aims to examine, for the first time, the complex influence of NPs and various pollutants on aquatic organisms during their early, stress-sensitive developmental stages (i.e., embryos, larvae, fry). We will determine the interactions of NPs with various pollutants and evaluate their effects based on NP size, shell type, and structure. The acquired results will be instrumental in elucidating the mechanisms of metal- and carbon-based NPs’ effects on aquatic organisms. It will also broaden the application possibilities of NPs in environmental protection and biomedicine.