Abstract: The crosstalk among pyroptosis, apoptosis, and necroptosis has facilitated the emergence of the innovative concept of PANoptosis. As a form of immunogenic cell death, PANoptosis is closely associated with various tumors through its unique regulatory mechanisms, thereby offering novel directions and insights for tumor immunotherapy. This review summarizes the mechanistic underpinnings of PANoptosis and the current evidence regarding its role in tumor progression. Furthermore, we discuss immunotherapeutic strategies targeting PANoptosis, with the aim of transitioning the research paradigm of tumor cell death from a unimodal to a multidimensional regulatory framework, and providing new perspectives for the clinical management of malignancies.