Tumor progression is accompanied by intrinsic heterogeneity and different phenotypes, which implies a different expression of cell surface receptors. Fibroblast activation protein (FAP) and integrin αvβ3 are highly expressed in the cell surface of cancer-associated cells or cancer cells compared with normal cells. Therefore, a FAP/integrin αvβ3 bispecific heterodimer was developed for positron emission tomography (PET) diagnostic imaging and radiotherapy. The heterodimer DOTA-FAPI-RGD was labeled with the diagnostic radionuclide gallium-68 or the therapeutic radionuclide lutetium-177, with yields >80%, and high stability. The competitive displacement binding assay showed an IC50 = 6.8 ± 0.6 nM for DOTA-FAPI-RGD towards FAP and IC50 = 2.1 ± 0.4 nM towards integrin αvβ3. Radionuclide labeled DOTA-FAPI-RGD showed high specificity and rapid internalization into U87MG cells (FAP/αvβ3-positive) in vitro. Micro-PET and biodistribution studies of [68Ga]Ga-DOTA-FAPI-RGD in tumor-bearing mice demonstrated that a high and specific tumor uptake of the tracer and a fast body clearance, resulting in high contrast images. In addition to the imaging applications demonstrated in this study, the labeling of the heterodimeric ligand with the radionuclide lutetium-177 used in cancer treatment might allow the therapeutic application of this ligand.