Abstract: “Omics” and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). ¹H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol^-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.