The FGFR signaling pathway is crucial for cellular functions such as proliferation, differentiation, and survival. Dysregulation of this pathway is linked to various cancers, making FGFR a key therapeutic target. This review summarizes the function, signaling pathways, and abnormalities of FGFR, as well as its role in tumorigenesis. It provides an analysis of phase 2 and 3 clinical trials evaluating FGFR inhibitors, highlighting four FDA-approved drugs and their molecular mechanisms and clinical achievements. The review discusses the challenges of targeting FGFR, including resistance mechanisms like gatekeeper mutations, alternative pathways, and adverse reactions. It emphasizes the potential of FGFR-targeted therapies to improve patient prognosis and the need for further research to overcome resistance and optimize treatment. FGFR consists of five members (FGFR1-5) and is involved in various biological processes, including embryonic development, angiogenesis, and tissue homeostasis. Abnormalities in FGFR signaling, such as gene amplification, mutations, and fusions, are prevalent in various cancers. FGFR1, FGFR2, FGFR3, and FGFR4 are frequently altered in different malignancies, with FGFR2 being most common in cholangiocarcinoma. FGFR3 mutations are prevalent in bladder cancer, and FGFR4 is involved in rhabdomyosarcoma. FGFR alterations are detected using methods like FISH, RT-PCR, NGS, and hybridization-capture. Liquid biopsy techniques allow for non-invasive detection of FGFR alterations in body fluids. Clinical trials have shown that FGFR inhibitors like infigratinib, pemigatinib, erdafitinib, and futibatinib demonstrate significant anti-tumor activity in various cancers. However, resistance mechanisms and adverse effects remain challenges. Selective FGFR inhibitors such as AZD4547, HMPL-453, RLY-4008, and others show promise in clinical trials. Multi-targeting TKIs like lenvatinib, surufatinib, nintedanib, anlotinib, and lucitanib have demonstrated efficacy in various cancers. Combination therapies with chemotherapy and other targeted therapies, as well as ICBs, are being explored to enhance therapeutic outcomes. While some combinations show promise, challenges remain in overcoming resistance and ensuring safety. Overall, FGFR-targeted therapies offer new hope for patients with FGFR-altered cancers, but further research is needed to optimize their use.The FGFR signaling pathway is crucial for cellular functions such as proliferation, differentiation, and survival. Dysregulation of this pathway is linked to various cancers, making FGFR a key therapeutic target. This review summarizes the function, signaling pathways, and abnormalities of FGFR, as well as its role in tumorigenesis. It provides an analysis of phase 2 and 3 clinical trials evaluating FGFR inhibitors, highlighting four FDA-approved drugs and their molecular mechanisms and clinical achievements. The review discusses the challenges of targeting FGFR, including resistance mechanisms like gatekeeper mutations, alternative pathways, and adverse reactions. It emphasizes the potential of FGFR-targeted therapies to improve patient prognosis and the need for further research to overcome resistance and optimize treatment. FGFR consists of five members (FGFR1-5) and is involved in various biological processes, including embryonic development, angiogenesis, and tissue homeostasis. Abnormalities in FGFR signaling, such as gene amplification, mutations, and fusions, are prevalent in various cancers. FGFR1, FGFR2, FGFR3, and FGFR4 are frequently altered in different malignancies, with FGFR2 being most common in cholangiocarcinoma. FGFR3 mutations are prevalent in bladder cancer, and FGFR4 is involved in rhabdomyosarcoma. FGFR alterations are detected using methods like FISH, RT-PCR, NGS, and hybridization-capture. Liquid biopsy techniques allow for non-invasive detection of FGFR alterations in body fluids. Clinical trials have shown that FGFR inhibitors like infigratinib, pemigatinib, erdafitinib, and futibatinib demonstrate significant anti-tumor activity in various cancers. However, resistance mechanisms and adverse effects remain challenges. Selective FGFR inhibitors such as AZD4547, HMPL-453, RLY-4008, and others show promise in clinical trials. Multi-targeting TKIs like lenvatinib, surufatinib, nintedanib, anlotinib, and lucitanib have demonstrated efficacy in various cancers. Combination therapies with chemotherapy and other targeted therapies, as well as ICBs, are being explored to enhance therapeutic outcomes. While some combinations show promise, challenges remain in overcoming resistance and ensuring safety. Overall, FGFR-targeted therapies offer new hope for patients with FGFR-altered cancers, but further research is needed to optimize their use.