In aquatic environment, engineered nanoparticles (ENPs) are present as complex mixtures with other pollutants, such as trace metals, which could result in synergism, additivity or antagonism of their combined effects. Despite the fact that the toxicity and environmental risk of the ENPs have received extensive attention in the recent years, the interactions of ENPs with other pollutants and the consequent effects on aquatic organisms represent an important challenge in (nano)ecotoxicology. The present review provides an overview of the state-of-the-art and critically discusses the existing knowledge on combined effects of mixtures of ENPs and metallic pollutants on aquatic organisms. The specific emphasis is on the adsorption of metallic pollutants on metal-containing ENPs, transformation and bioavailability of ENPs and metallic pollutants in mixtures. Antagonistic, additive and synergistic effects observed in aquatic organisms co-exposed to ENPs and metallic pollutants are discussed in the case of “particle-proof” and “particle-ingestive” organisms. This knowledge is important in developing efficient strategies for sound environmental impact assessment of mixture exposure in complex environments