Improving therapeutic efficacy and antitumor immune responsiveness in BRCA1-mutant ovarian cancer remains challenging. Here, we developed a BRCA1 mutation-guided tetrahedral framework nucleic acid nanosystem, FBOA-tFNA, for coordinated intracellular delivery of the PARP inhibitor olaparib and the WEE1 inhibitor adavosertib. After folate receptor-mediated uptake, FBOA-tFNA recognizes BRCA1 mutant RNA through toehold-mediated strand displacement, enabling mutation-selective beacon activation, while drug release is independently regulated by reduction-responsive disulfide cleavage. Coordinated PARP/WEE1 inhibition amplified DNA damage, impaired G2/M checkpoint protection, and promoted tumor-cell killing in BRCA1-mutant ovarian cancer models. Resulting DNA damage-associated intracellular dsDNA signals activated STING-associated signaling, type I interferon responses, immunogenic cell death (ICD)-associated stress, dendritic-cell maturation, and CD8+ T-cell activation. Engineered patient-derived ovarian cancer organoids expressing a BRCA12594delC-containing transcript further supported the mutation-selective recognition and therapeutic potential of FBOA-tFNA ex vivo. In vivo, FBOA-tFNA showed tumor-associated fluorescence accumulation, BRCA1 mutant-transcript recognition-associated beacon activation, enhanced antitumor efficacy, and preliminary repeated-dose tolerability. Moreover, FBOA-tFNA enhanced antitumor immune responses and improved the response to anti-PD-1 therapy, accompanied by increased effector and memory-like T-cell populations. This programmable DNA nanoplatform provides a personalized combination strategy for coordinated DNA-damage therapy and immunomodulation in BRCA1-mutant ovarian cancer.