Biomedical application of various nanoparticles (NPs) for bioimaging and therapeutic purposes attracts huge interest. In particular, NPs can be used as nanocarriers of radionuclides for radiotherapy of malignant neoplasms. However, most approaches for NP radiolabeling are complicated, and their transfer into clinical practice is difficult due to their multistep process, limited reproducibility, and lack of an automated radiolabeling procedure. Here, we develop a universal method suitable for radiolabeling of various NPs (either organic or inorganic) for internal radiotherapy of B16-F10 melanoma tumors. The obtained NPs (polylactide, silica, gold, and iron oxide) were labeled with diagnostic (99mTc) and therapeutic (188Re) radionuclides with a high radiolabeling efficiency (∼94–98%) and radiochemical stability (>95%). After their intratumoral administration, these various 188Re-labeled NPs mostly remained in the tumor, inhibiting the tumor growth rate compared to the untreated tumors. The absence of any significant leakage of the radiolabeled NPs in healthy tissues (the liver, heart, kidneys, lungs, and spleen) was confirmed by single-photon emission computed tomography (SPECT) and direct radiometry analysis. Histological analysis revealed no abnormal changes in healthy organs after the therapy (e.g., no acute pathologic findings were detected in the liver and kidneys). As a result, the treatment of mice with 188Re-labeled NPs led to a prolonged survival compared to the control group. Thus, our study provides general guidance for the use of different types of radiolabeled NPs in radionuclide therapy.