A retrospective cohort study reports a significant kidney injury risk increase when vancomycin is combined with piperacillin-tazobactam in cancer patients. Compared with vancomycin alone, the combination was associated with a fourfold higher risk of acute kidney injury. The data targets a common real-world escalation pattern in oncology supportive care, where broad-spectrum coverage can be clinically compelling but nephrotoxicity consequences are a major management concern. For clinicians and clinical teams, the results reinforce the need for antibiotic stewardship and risk-based selection in cancer populations, especially for patients already at baseline renal vulnerability. The study design is observational, so causal certainty is limited; however, the magnitude of the reported association raises urgency for institutional protocols and monitoring practices.