Multifunctional micelles loaded with the near-infrared (NIR) dye and labeled with the radionuclide rhenium-188 ((188)Re) have been developed to provide multimodalities for NIR fluorescence and nuclear imaging and for photothermal therapy (PTT) of cancer. The NIR dye, IR-780 iodide, allowed the micelles to have dual functions in cancer NIR imaging and PTT. The (188)Re-labeled IR-780 micelles enabled imaging by NIR fluorescence and by microSPECT to guide the delivery of drugs and to monitor in real-time the tumor accumulation, intratumoral distribution, and kinetics of drug release, which serve as a basis of specific photothermal injury to the targeted tissue. We also investigated the biodistribution, generation of heat, and photothermal cancer ablation of IR-780 micelles of both in vitro and in vivo xenografts. Histopathology observed irreversible tissue damage, such as necrotic features, decreased cell proliferation, increased apoptosis of cells, and increased expression of heat shock proteins in the PTT-treated tumors. The (188)Re-labeled IR-780 micelles offer multifunctional modalities for NIR fluorescence and nuclear imaging and for PTT of cancer.