This article examines the clinical and translational application of specific next-generation blood-brain barrier penetrant KRAS<sup>G12C</sup> inhibitors, such as sotorasib, adagrasib, olomorasib, RMC-6236, and D3S-001, and their rational integration with radiation therapy, targeted therapies, and immunotherapies to overcome therapeutic resistance in patients with NSCLC brain metastases. Here, KRAS is linked to non-small cell lung carcinoma.