A multifunctional FePt nanoparticle was developed that targets tumor microvasculature via "radiation-guided" peptides, and is detected by both near-infrared (NIR) fluorescence imaging and analytical mass spectrometry methods. Tumor specific binding was first measured by biotinylated peptide linked to fluorophore-conjugated streptavidin. This showed tumor selective binding to tumors using the HVGGSSV peptide. FePt nanoparticles were synthesized sequentially by surface modification with poly(L)lysine, poly(ethylene) glycol conjugation, and functionalized with HVGGSSV peptide and fluorescent probe Alexa fluor 750. NIR fluorescence imaging and ICP-MS analysis showed significant HVGGSSV-FePt nanoparticle binding to irradiated tumors as compared to unirradiated tumors and controls. Results indicate that multifunctional FePt nanoparticles have potential application for radiation-guided targeting and imaging of cancer.