Significant progress has been made in targeting liver and bladder malignancies. Identification of S100A4’s role in driving hepatocellular carcinoma metastasis via interaction with NMIIA elucidates a novel mechanism of invasiveness. Differentiation therapy employing HNF4α to reprogram malignant liver cells offers a promising new treatment angle. In bladder cancer, the transcription factor TCF3 promotes tumor progression through a ferroptosis-dependent TMBIM6-Ca²⁺ pathway. Collectively, these findings provide new molecular targets for intervention in aggressive cancers with poor prognoses.