However, partial necrosis flap in the potential territory remains a challenge to plastic surgeons. We raised a novel “hybrid nourished mode” (HNM) flap based on the multiterritory deep inferior epigastric perforator (DIEP) flap to improve flap survival. Thirty-two rabbits were randomly divided into DIEP and HNM groups. Untargeted metabolic mechanisms between the DIEP and HNM groups were performed using LC-MS under the filter criteria of fold change >20.0 times or <0.05, and variable importance value (VIP) was set at ≥1, p<0.05. Between the two groups, flap survival, perfusion, microvasculature, histopathology, and immunohistochemistry of CD31 were assessed on postoperative day 7. We screened 16 different metabolites that mainly participated in Biosynthesis of secondary metabolites, Aminoacyl-tRNA biosynthesis, Phenylalanine metabolism, Arginine and proline metabolism and so on. The results of the HNM flaps were higher than those of DIEP flaps (p<0.05) in the aspect of flap survival, flap perfusion, and microvasculature. Compared with the DIEP flaps, HNM has a stronger advantage in tissue metabolism. This study provided us with a better understanding and strong evidence in terms of metabolites on how HNM achieves the survival of large multiterritory perforator flaps.