Cancer is the second leading cause of death in the United States and accounts for approximately one in every four deaths. Employing theranostic nanoprobes, which combine both diagnostic and therapeutic capabilities, has promise to propel the biomedical field toward personalized cancer medicine. CD13 receptor is an important regulator of endothelial morphogenesis during tumor angiogenesis − a vital biomarker in tumor growth and metastatic spread. Herein, we propose a new strategy for individualized diagnosis and treatment of cancer by developing novel multifunctional gold nanostars (GNS), which combine features for CD13-targeted multimodality [positron emission tomography (PET), computed tomography (CT), ultrasound (US), photoacoustic (PA)] imaging and photothermal therapy. Combinations of imaging techniques, as socalled “multimodality imaging”, such as PET/CT/US/PA imaging, are being designed with the purpose of taking advantage of the strengths while overcoming the weaknesses of each modality, which as a result may accurately and simultaneously provide anatomical and functional information. For instance, sensitive PET imaging can be used to quantify the CD13 expression level, while the US/PA imaging is able to combine optical and acoustic information to decipher tumor microenvironment. Based on our promising preliminary results, we hypothesize that our new chelator system and strain-promoted catalyst-free click chemistry approach could provide a reliable kit-like method for the fast construction of biocompatible, multimodal, and theranostic GNS probes. The Specific Aims of this project address important questions regarding the preclinical evaluations of multifunctional GNS.