Plastic production began in the early 1900s and it has transformed our way of life. Despite the many advantages of plastics, a massive amount of plastic waste is generated each year, threatening the environment and human health. Because of their pervasiveness and potential for health consequences, small plastic residues produced by the breakdown of larger particles have recently received considerable attention. Plastic particles at the nanometer scale (nanoplastics) are more easily absorbed, ingested, or inhaled and translocated to other tissues and organs than larger particles. Nanoplastics can also be transferred through the food web and between generations, have an influence on cellular function and physiology, and increase infections and disease susceptibility. This review will focus on current research on the toxicity of nanoplastics to aquatic species, taking into account their interactive effects with complex environmental mixtures and multiple stressors. It intends to summarize the cellular and molecular effects of nanoplastics on aquatic species; discuss the carrier effect of nanoplastics in the presence of single or complex environmental pollutants, pathogens, and weathering/aging processes; and include environmental stressors, such as temperature, salinity, pH, organic matter, and food availability, as factors influencing nanoplastic toxicity. Microplastics studies were also included in the discussion when the data with NPs were limited. Finally, this review will address knowledge gaps and critical questions in plastics’ ecotoxicity to contribute to future research in the field.