Future clinical trials that assess the combination of PLK1 inhibitors with antiangiogenic agents already part of the standard-of-care in advanced NSCLC, such as bevacizumab or ramucirumab, or next-generation drugs, including multikinase inhibitors such as lenvatinib, would fit with the current unmet need of effective treatment strategies after the failure of platin-based chemotherapy and immune checkpoint inhibitors, possibly integrating assessment of tissue-based biomarkers including PLK1 expression. Here, PLK1 is linked to non-small cell lung carcinoma.