Once labeled “undruggable,” KRAS has emerged as one of oncology’s most promising—yet complex—targets. With nearly 90% of pancreatic cancers and 30-40% of lung and colorectal cancers harboring KRAS mutations, the need for effective therapies is urgent. Recent FDA approvals of KRAS G12C inhibitors have signaled a new era, but the rise of resistance and diverse mutation profiles demand deeper innovation. As preclinical tools and combination strategies evolve, scientists must ask: how do we stay ahead of KRAS-driven resistance and translate insights into patient-specific treatment success?