Abstract: Metabolic abnormality is one of the remarkable characteristics that distinguish tumor tissues from normal tissues. Intervening in the specific targets of abnormal metabolism in tumor cells is an important strategy for tumor treatment. The major function of isocitrate dehydrogenase 1 (IDH1), a key rate-limiting enzyme in the tricarboxylic acid cycle, is to catalyze the conversion of isocitrate to α-ketoglutaric acid (α-KG). However, mutant IDH1 (mIDH1) can further convert α-KG into D-2-hydroxyglutarate (D-2-HG), a carcinogenic metabolite, thus inducing the occurrence and development of tumors. Currently, quite a few mIDH1 inhibitors have entered the clinical trial stage, and three have been approved for marketing. However, the problem of acquired resistance has also been observed clinically. The main indications of mIDH1 inhibitors are acute myeloid leukemia and glioma. For other solid tumors carrying mIDH1 mutations, effective inhibitors are still relatively scarce. In recent years, as an effective means to improve drug sensitivity, reduce adverse reactions and overcome drug resistance, synergistic therapy has been widely applied for tumor treatment. This article reviews IDH1-related cancers and other diseases, focusing on the research progress of clinical small molecule inhibitors and their combination with other anti-tumor drugs for synergistic therapy, aiming to help deepen the comprehensive understanding of this field and provide some reference for further development of synergistic anti-tumor strategies.