The presented literature review provides up-to-date information on the oncosuppressive effects of exogenous nucleases derived from various sources. Exogenous nucleases, such as RNaseA, BS-RNase, onconase, and DNaseI, have the ability to degrade low-molecular-weight extracellular DNA and RNA circulating in blood plasma, which may significantly reduce the risk of metastasis. The role of extracellular DNA and RNA in oncogenesis, as well as the impact of exogenous nucleases on their quantity, is described. The prospects of using nucleases in combination with other therapeutic methods, such as chemotherapy and radiotherapy, to enhance their effectiveness and reduce side effects, are discussed. Additionally, the targets and mechanisms of action of nucleases, as well as the possibility of their combined use with other therapeutic agents, are considered. A conclusion is drawn about the potential effectiveness of exogenous nucleases in cancer therapy.