Parasitoid wasps, shaped by ecological pressures and interspecific competition, have evolved sophisticated molecular strategies to manipulate host physiology, ensuring successful parasitism and optimal progeny development. Despite substantial advances in parasitoid–host interaction research, a systematic synthesis of these findings is still lacking. This review aims to consolidate recent findings on the molecular mechanisms by which endoparasitoids regulate host physiology, and to explore their potential applications in sustainable pest management. We reviewed recent progress on virulence factors derived from venom, polydnaviruses, and teratocytes, focusing on their roles in immune suppression, developmental regulation, and metabolic reprogramming of insect hosts. Three principal mechanisms underlying parasitoid-mediated host manipulation are identified: (1) Immune suppression: Parasitoids reduce hemocyte abundance, disrupt hemocyte mobilization to impede encapsulation, inhibit phenoloxidase activation to prevent melanization, and interfere with immune signaling pathways. Some species also adopt passive immune evasion strategies. (2) Developmental regulation: Parasitoids delay host growth and metamorphosis by downregulating ecdysteroid titers, inhibiting cell proliferation, degrading host tissues, and repressing protein synthesis. (3) Metabolic reprogramming: Parasitoids manipulate host amino acid, carbohydrate, and lipid metabolism to mobilize and redirect nutritional resources toward their developing offspring. This review offers a comprehensive overview of the molecular tactics employed by endoparasitoids to modulate host physiology. By elucidating these mechanisms, we propose parasitoid-derived virulence factors as promising leads for developing novel, sustainable pest control strategies.
