BACKGROUND: Immune checkpoint inhibitors (ICI) have changed the management of cancer dramatically. However, not all patients respond to ICI and their use places patients at a significant risk of immune-related adverse reactions. A few biomarkers including programmed death-1 receptor/programmed death-ligand 1 (PD-1/PD-L1), micro-satellite instability (MSI) status, and tumor mutational burden (TMB) have gained popularity as surrogates to predict responsiveness to ICI. CASE REPORT: Herein, we report a 61-year-old male who was diagnosed with widespread metastatic adenocarcinoma and a discrete renal lesion. Most of the metastatic lesions, except the left kidney mass, responded to a combination immunotherapy. Subsequent left nephrectomy revealed a chromophobe renal cell carcinoma. With this multimodality approach, we were able to achieve a durable near complete remission in a patient with diffuse metastatic disease at diagnosis. CONCLUSION: In this report, we explored possible commercially available and experimental biomarkers in an attempt to explain his exceptional response.