Abstract: Nanoparticle-assisted ultrasound therapy (NAUT) employs low-frequency ultrasound to in situ activate gold nanoparticles, generating cavitation- and sonodynamic-derived reactive oxygen species that elicit immunogenic cell death and convert the immunologically “cold” triple-negative breast cancer (TNBC) microenvironment into a “hot” phenotype. Benefiting from its physical targeting precision, minimal invasiveness, and potent immuno-sensitization, NAUT surpasses conventional chemotherapy or single-agent immune checkpoint inhibitors in overcoming TNBC heterogeneity and eradicating minimal residual disease. In this review, the mechanistic advances of NAUT are summarized, the design of smart nanoplatforms is highlighted, its synergistic efficacy with immune checkpoint inhibitors is evaluated, and the clinical potential and challenges of NAUT in eradicating minimal residual disease are discussed. This review offers a new paradigm for precision physical-immunotherapy of TNBC.