Indisulam is primarily investigated for its antitumor activity, particularly in the treatment of various cancers. It functions as a sulfonamide-based anticancer agent that modulates cell cycle progression by inducing G1 arrest in tumor cells. Its mechanism involves binding to the protein RBM39 through recruitment to the CUL4–DCAF15 E3 ubiquitin ligase complex, leading to targeted degradation of RBM39, which disrupts RNA splicing in cancer cells. This selective splicing modulation is especially effective in hematologic malignancies and certain solid tumors. It has shown promising results in preclinical and clinical studies for cancers such as acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and non-small cell lung cancer (NSCLC). Indisulam’s efficacy appears to be higher in tumors expressing high levels of DCAF15, making it a candidate for precision oncology approaches. Ongoing research focuses on identifying biomarkers to predict response and improving its therapeutic window through combination regimens with other anticancer agents.