Global industrialization has led to the intoxication of natural ecosystems with heavy metals and their derivatives at various scales impacting the biogeochemical cycles across the planet. Cultivation of food crops in such heavy metal-intoxicated soil and water sources poses deleterious effects on our naturally built homeostasis. Developments in synthetic biology and genetic engineering allow organisms to be engineered to have improved detoxifying capacities. Enzyme engineering makes it easier to create optimal biocatalysts by applying directed evolution and rational design. In detoxification techniques, the inclusion of nanotechnology—including nanostructured materials and nanoparticles—improves adsorption, catalysis and targeted delivery. Omics technologies guide the discovery of important genes and pathways by providing a thorough understanding of molecular mechanisms. The chapter discusses the development of advanced technologies for bioremediation/biological detoxification of metals, metalloids and radionuclides.