Abstract: Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) targeted therapy as a novel immunotherapy has changed the treatment landscape of many cancers, yet only a subset of patients can benefit from clinical treatment. One of the influencing factors is the level of tumor PD-1/PD-L1 expression. Molecular imaging of non-invasive nuclide drugs may provide a potential solution to how to achieve non-invasive dynamic monitoring of them in vivo. PD-1/PD-L1 targeted imaging with radionuclidelabeled intact monoclonal antibodies, antibody fragments, or peptides and other probes can monitor systemic PD-1/PD-L1 expression dynamically in real time, providing an effective means to screen potential beneficiaries, predict treatment efficacy and prognosis, and guide PD-1/PD-L1-targeted therapy in real time, non-invasively, and dynamically during immunotherapy. This review introduces the application of monitoring and efficacy assessment of radiolabeled protein-based drugs in PD-1/PD-L1-targeted immunotherapy to provide a basis for future clinical transformation and optimization of new radioactive protein diagnosis and treatment drugs.