Targeting metabolic enzymes, such as pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDHA), glutaminase (GLS), and monocarboxylate transporters (MCT-1), alongside immune checkpoint inhibitors or IDO1 blockade, presents a promising strategy for overcoming metabolic plasticity and immune evasion in Wnt-driven malignancies, thereby enhancing therapeutic efficacy and improving patient survival in otherwise refractory tumor types. The gene discussed is PDK1; the disease is neoplasm.