This systematic review highlights that PD-1 and PD-L1 overexpression, when used in combination with immune checkpoint inhibitor (ICI) therapy, could represent a cost-effective strategy for treating NSCLC as a first-line treatment with pembrolizumab and with both first- and second-line nivolumab, but also for renal cell and urothelial carcinoma. Here, CD274 is linked to urothelial carcinoma.