Heavy metals (HMs) and metalloid occur naturally and are found throughout the Earth's crust but they are discharged into aquatic environments at high concentrations by human activities, increasing heavy metal pollution. HMs can bioaccumulate in higher organisms through the food web and consequently affect humans. In an aquatic environment, various HMs mixtures can be present. Furthermore, HMs adsorb on other environmental pollutants, such as microplastics and persistent organic pollutants, causing a synergistic or antagonistic effect on aquatic organisms. Therefore, to understand the biological and physiological effects of HMs on aquatic organisms, it is important to evaluate the effects of exposure to combinations of complex HM mixtures and/or pollutants and other environmental factors. Aquatic invertebrates occupy an important niche in the aquatic food chain as the main energy link between higher and lower organisms. The distribution of heavy metals and the resulting toxic effects in aquatic invertebrates have been extensively studied, but few reports have dealt with the relationship between HMs, pollutants, and environmental factors in biological systems with regard to biological availability and toxicity. This review describes the overall properties of individual HM and their effects on aquatic invertebrates and comprehensively reviews physiological and biochemical endpoints in aquatic invertebrates depending on interactions among HMs, other pollutants, and environmental factors.