Immunotherapy has revolutionized the modality for establishing a firm immune response and immunological memory. However, intrinsic limitations of conventional low responsive poor T cell infiltration and immune related adverse effects urge the coupling of cancer nanomedicines with immunotherapy for boosting antitumor response under ultrasound (US) sensitization to mimic dose-limiting toxicities for safe and effective therapy against advanced cancer. US is composed of high-frequency sound waves that mediate targeted spatiotemporal control over release and internalization of the drug. The unconventional US triggered immunogenic nanoengineered arena assists the limited immunogenic dose, limiting toxicities and efficacies. In this Review, we discuss current prospects of enhanced immunotherapy using nanomedicine under US. We highlight how nanotechnology designs and incorporates nanomedicines for the reprogramming of systematic immunity in the tumor microenvironment. We also emphasize the mechanical and biological potential of US, encompassing sonosensitizer activation for enhanced immunotherapeutic efficacies. Finally, the smartly converging combinational platform of US stimulated cancer nanomedicines for amending immunotherapy is summarized. This Review will widen scientists' ability to explore and understand the limiting factors for combating cancer in a precisely customized way.