Ulixertinib is a potent and selective inhibitor of the extracellular signal-regulated kinase (ERK) pathway, which plays a central role in the RAS/RAF/MEK/ERK signaling cascade. This pathway is frequently dysregulated in various cancers due to mutations in genes such as BRAF, RAS, or upstream receptors, leading to uncontrolled cell proliferation and survival. By inhibiting ERK1 and ERK2, ulixertinib effectively blocks downstream signaling in this oncogenic pathway, making it a promising therapeutic agent for tumors resistant to upstream inhibitors like BRAF or MEK inhibitors. It has shown clinical activity in patients with advanced solid tumors harboring MAPK pathway alterations, particularly in melanoma, non-small cell lung cancer, and colorectal cancer. Because ulixertinib acts downstream in the pathway, it may overcome resistance that develops with BRAF or MEK inhibitor treatments. This makes it a valuable option in settings where tumors have acquired resistance through reactivation of the MAPK pathway. Ulixertinib is being investigated in clinical trials both as a monotherapy and in combination with other targeted agents, aiming to improve response rates and delay disease progression. Its development represents a strategy to target the MAPK pathway more completely and to address one of the major challenges in precision oncology—treatment resistance.