Sonothermal therapy for cancer involves using ultrasound in combination with nanoparticles to generate heat selectively within tumor tissues, leading to hyperthermia and subsequent destruction of cancer cells. This article exhibits the combined effect of ultrasound and NIR irradiation-mediated thermal ablation of melanoma skin cancer cell lines (B16). The dually responsive nanoparticles are constructed from a ferric-tannic coordination complex, which has been an excellent photothermal agent in many prior investigations. However, to our knowledge, the dual stimuli of ultrasound and NIR have not been applied to ferric-tannic nanoparticles (FeTA NPs). These dually responsive FeTA NPs exhibited enhanced temperature rise compared to US or NIR irradiation alone and caused significant cell death, reactive oxygen species generation, and mucin binding efficacy. Thus, the US/NIR synergistic effect on FeTA NPs could be a promising approach for improved cancer treatment outcomes.