The present study describes a rare case of plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML). A 70-year-old male patient was diagnosed with pDC-AML and underwent induction chemotherapy using the venetoclax + azacitidine (VA) regimen. After 3 weeks of treatment, bone marrow examination indicated a morphologic leukemia-free state (MLFS); however, the patient experienced persistent cytopenia, which was further complicated by severe pneumonia and gastrointestinal bleeding, both of which improved following treatment. After 3 weeks in MLFS, bone marrow morphology and minimal residual disease analysis revealed a relapse of leukemia. The patient subsequently underwent treatment with selinexor in conjunction with the VA regimen; however, due to severe thrombocytopenia, the family decided to discontinue further treatment. The patient subsequently succumbed shortly after discharge. pDC-AML is an extremely rare disease characterized by low complete remission rates and a poor prognosis. While the VA regimen demonstrates rapid efficacy and favorable safety in elderly patients, especially those unable to tolerate intensive chemotherapy, the risk of relapse remains substantial. CD123-targeted therapies may present potential new therapeutic options for this disease. Improving remission rates and extending survival in patients with pDC-AML remain pressing clinical challenges.