Abstract: Advanced metastatic penile squamous cell carcinoma (PSCC) is a rare and highly aggressive malignancy, for which current guidelines have not reached a consensus on second-line treatment, making clinical management extremely challenging. The effectiveness of immune checkpoint therapy for metastatic PSCC is very limited. Exploring new approaches to enhance the efficacy of immunotherapy is crucial, and the triple therapy of stereotactic body radiotherapy (SBRT) combined with Programmed Cell Death Protein 1 Inhibitor (PD-1 inhibitor) and granulocyte-macrophage colony-stimulating factor (GM-CSF), abbreviated as PRaG, may be a promising treatment strategy. The case report examines the efficacy of PRaG therapy (SBRT combined with PD - 1 inhibitor and GM-CSF) in advanced metastatic penile squamous cell carcinoma (PSCC), a rare and aggressive malignancy with no consensus on second-line treatment. A 65-year-old male, diagnosed with PSCC in December 2020 and having multiple metastases after recurrence in May 2021, showed disease progression again in December 2021 following first-line chemotherapy. Administered PRaG therapy due to lack of standard subsequent treatments per NCCN guidelines, the patient exhibited remarkable sensitivity with targeted radiation and abscopal effects. The patient underwent three sessions of PRaG therapy, achieving favorable therapeutic outcomes and mild side effects. PRaG therapy may provide an alternative for the treatment of patients with advanced recurrent or refractory cancer.