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Simple Summary: Triple-negative breast cancer is an aggressive malignancy with a poor prognosis. Nanosecond pulsed electric field is a new method for local tumor ablation. However, the mechanism of nanosecond pulsed electric field therapy for triple-negative breast cancer is not clear. We constructed a mouse model of triple-negative breast cancer. Transcriptome sequencing and other techniques were used. We demonstrated that nanosecond pulsed electric field effectively ablated tumor and induced apoptosis related pathways. Nanosecond pulsed electric field ablation activated tumor immunity and promoted the infiltration of CD8+ T cells. The inhibition of residual cancer growth mediated by nanosecond pulsed electric field ablation was dependent on CXCL9 axis. Triple-negative breast cancer (TNBC) is a refractory tumor, and therapeutic options are very limited. Local ablation has been applied recently. Chemokines play a critical role in the recruitment of immune cells into ablative tumors. Nanosecond pulsed electric field (nsPEF) shows potential anti-tumor efficacy, but the mechanism for maintaining the immune effect is not very clear. Here, we applied nsPEF for treating 4T1 breast cancer cells in vitro. RNA sequencing (RNA-seq) was applied. Anti-CXCL9 was used alone or combined with nsPEF to treat triple-negative breast cancer in mice. We demonstrated that nsPEF effectively induced cell apoptosis and inhibited the growth and metastasis of triple-negative breast cancer. An immune effect, especially chemotaxis, was activated by nsPEF. The number of infiltrated CD8+ T cells was increased significantly. We found that the inhibition of residual breast cancer growth by nsPEF was dependent on the CXCL9 axis. In conclusion, our work demonstrated that nsPEF effectively ablated the tumor, aroused an immune response, and inhibited residual breast cancer growth via CXCL9 axis dependence in mice. [ABSTRACT FROM AUTHOR]