Novel therapeutic strategies that can effectively combine with immunotherapies are needed in the treatment of triple-negative breast cancer (TNBC). Here, we show that the PARP inhibitor Olaparib and the WEE1 inhibitor AZD1775 (adavosertib) interact synergistically in BRCA1/2 wildtype TNBC models to induce replication stress and induce effective anti-tumor activity. Given that Olaparib and AZD1775 have overlapping toxicity profiles (1), we have assessed the efficacy of combining lower doses of both olaparib and AZD1775 in this study. The combined treatment induced an anti-tumor inflammatory immune response which increased tumor infiltration and activation of CD4 and CD8 T cells as well as cytotoxic T cell-mediated clearance of tumor cells. Depletion of both T cell subsets abolished the anti-tumor efficacy of combined DDR inhibitor treatment. The addition of anti-PD-1 enhanced the efficacy of PARP and WEE1 inhibition in an immunogenic preclinical model of TNBC but conferred no further benefit to the anti-tumor activity of combined DDR inhibition in poorly immunogenic AT3 and 4T1ch9 models. Combined DDR inhibition with STING agonist resulted in durable tumor regression and significant improvements of survival outcomes in multiple tumor models of TNBC. These findings provide insight into a novel mechanism of action of PARPi and WEE1i in BRCA1/2-wildtype TNBC, and rationale for harnessing the anti-tumor immune responses of DDR inhibitors to potentiate the therapeutic efficacy of immunotherapies to improve patient outcomes.