There are limited reports of concomitant infection with hepatitis B virus, Epstein-Barr virus, and cytomegalovirus. This case represents the first documented instance of such a triple infection in an individual with metastatic renal cell carcinoma undergoing combined immunotherapy with ipilimumab and nivolumab. This is the case of a 40-year-old male patient with past medical history notable for type 1 diabetes mellitus and renal cell carcinoma who exhibited liver function abnormalities suggestive of viral liver injury, particularly due to hepatitis B virus reactivation. Interestingly, despite the triple infection, the patient experienced relatively mild disease progression, with liver function tests showing a downward trend, likely due to timely intervention with tenofovir. This case highlights the complexity of viral interactions in immunocompromised patients and emphasizes the need for further research into optimal management strategies.