The emerging combination of chemotherapy and radionuclide therapy has been actively investigated to overcome the limitations of monotherapy and augment therapeutic efficacy. However, it remains a challenge to design a single delivery vehicle that can incorporate chemotherapeutics and radionuclides into a compact structure. Here, a chelator DOTA- or NOTA-modified Evans blue conjugated camptothecin molecule (EB-CPT) nanoprodrug was synthesized, which could self-assemble into nanoparticles due to its inherent amphiphilicity. The nanoparticles could then be effectively labeled with therapeutic radionuclide lutetium-177 (Lu) or diagnostic radionuclides gallium-68 (Ga)/copper-64 (Cu) with high radiolabeling efficiency and radiochemical stability. Impressively, a single-dose chemoradiation therapy of [Lu]Lu-DOTA-EB-CPT plus EB-CPT effectively inhibited tumor growth in HCT116 tumor-bearing mice compared to the respective individual therapeutic approach. The [Cu]Cu-NOTA-EB-CPT nanoparticles also exhibited excellent in vivo characteristics including favorable blood circulation properties and prolonged tumor retention in tumor-bearing mice. The safety, feasibility, tolerability, and biodistribution of [Ga]Ga-NOTA-EB-ss-CPT were also preliminarily characterized in a first-in-human study. This study presents a simple but robust EB-CPT radiopharmaceutical that leverages EB as an albumin binder to strike a delicate balance between enhanced tumor accumulation, safety, and diagnostic efficacy, facilitating an integrated theranostic strategy within a single molecular structure. This radionuclide-labeled EB-CPT nanomedicine presents a step toward clinical translation of the combination of chemotherapy and radiotheranostics.