Mercury is a hazardous heavy metal that is distributed worldwide in aquatic ecosystems. Methylmercury (MeHg) poses significant toxicity risks to aquatic organisms, primarily through bioaccumulation and biomagnification, due to its strong affinity for protein thiol groups, which results in negative effects even at low concentrations. MeHg exposure can cause various physiological changes, oxidative stress, neurotoxicity, metabolic disorders, genetic damage, and immunotoxicity. To assess the risks of MeHg contamination in actual aquatic ecosystems, it is important to understand how MeHg interacts with environmental factors such as temperature, pH, dissolved organic matter, salinity, and other pollutants such as microplastics and organic compounds. Complex environmental conditions can cause potential toxicity, such as synergistic, antagonistic, and unchanged effects, of MeHg in aquatic organisms. This review focuses on demonstrating the toxic effects of single MeHg exposure and the interactive relationships between MeHg and surrounding environmental factors or pollutants on aquatic organisms. Our review also recommends further research on biological and molecular responses in aquatic organisms to better understand the potential toxicity of combinational exposure.