Nectin-4/PVRL-4 is overexpressed in tumors, driving proliferation and invasion. It's a key target for solid tumor therapy. Current tumor imaging methods are inadequate. Studying nectin-4 in lung cancer helps identify diagnostic biomarkers and develop radionuclide probes, intraoperative visualization,and new chemotherapies. High nectin-4 expression in lung cancer tissues was confirmed using TCGA data and IHC. Three optical probes targeting nectin-4 were synthesized. Optimal binding conditions were explored, and binding rates were assessed. Animal experiments showed the probes' specificity and biodistribution. The probes effectively targeted nectin-4, with Cy5.5-nectin-4 PEP 02 showing the highest binding rate. In vivo, the probe targeted lung cancer tissues, indicating potential for intraoperative navigation. Nectin-4 is a promising target for lung cancer and intraoperative navigation, guiding further research.