This chapter delves into the aquatic ecotoxicology of emerging contaminant mixtures, emphasizing the complexity of chemical interactions and their environmental impacts. It focuses on the combined effects of multiple pollutants, which often result in synergistic or antagonistic interactions, challenging traditional approaches that consider individual substances. The chapter begins by exploring fundamental concepts such as synergism, antagonism, additive toxicity, bioavailability, toxicokinetics, and toxicodynamics, providing a robust theoretical foundation. Detailed case studies illustrate the ecotoxicological effects of contaminant mixtures on aquatic organisms, underscoring the necessity of considering these complex interactions for accurate risk assessment. Advanced scientific tools, including adverse outcome pathways (AOPs), in vitro methods, quantitative structure-activity relationships (QSARs), and omics approaches, are discussed to demonstrate how they enhance the predictability and relevance of ecotoxicological studies. The chapter also addresses research challenges, such as organismal response variability and difficulty of replicating environmental conditions in the laboratory. Future perspectives highlight the need for long-term studies and the inclusion of a broader range of species, and it is the audience’s active involvement that will make these crucial for achieving a more comprehensive understanding of ecotoxicological risks. The significance of this chapter lies in its integrative and multidisciplinary approach, offering a comprehensive view of the impacts of emerging contaminant mixtures, thus contributing to the advancement of aquatic ecotoxicology and the formulation of effective environmental policies.