His research interests lie in the fields of radiochemistry, radiochemical technology, and radiopharmaceutical chemistry. He is a specialist in radionuclide separation and fractionation methods, radioactive waste disposal, radionuclide behavior in the geological environment, and the production of medical-grade radionuclides and derived radiopharmaceuticals. The body of work produced by S. N. Kalmykov and his colleagues—focusing on the role of colloidal particles in radionuclide migration in the environment, as well as the formation, structure, and properties of plutonium-bearing nanoparticles—is pioneering in nature. He is the developer of technologies for producing and isolating a number of medical-grade radionuclides from accelerator-irradiated targets.