Heavy metal exposure has soared due to the twentieth century's industrial activity. The most common heavy metals that lead to human poisoning are mercury, cadmium, and arsenic. Acute or chronic poisoning may develop following exposure to water, air, or food, so the bioaccumulation of these heavy metals causes harmful consequences in various human tissues and organs. Heavy metals interfere with biological functions such as growth, proliferation, differentiation, damage repair, and apoptosis. The mechanisms of action for these metals to cause toxicity are similar, including forming reactive oxygen species (ROS), weakening antioxidant defenses, enzyme inactivation, and oxidative stress. Heavy metal exposure is mainly associated with skin, liver, prostate, lung, urinary bladder, thyroid, and kidney cancers, as well as causing gastrointestinal malignancies. Several microRNAs (miRNAs or miRs) have been involved in various human cancers due to the dysregulation of miRNA function. Recent investigations have confirmed that microRNA dysregulation plays a role in the carcinogenesis of many tissues. This review presents the data concerning arsenic, cadmium, and mercury metals and their contamination sources, human exposure, toxicity, and inducing malignant transformations such as carcinogenicity in in-vitro or in-vivo specimens or dysregulated expression of microRNAs.