Flavour precursors are the basis of meat flavour, and their metabolism is regulated by a variety of enzymes. Thus, it is of great significance to identify the key genes related to meat flavour precursors. In this study, the difference in flavour precursors and transcriptome between Hu sheep and Dorper with different intramuscular fat (IMF) content were investigated using widely targeted metabolomics and RNA-sequencing technologies. Then, the key genes regulating the metabolism of vital precursors were explored by integrating transcriptome and metabolome. Consequently, 594 metabolites were detected in sheep longissimus dorsi, and 76 differentially abundant metabolites (DAMs) were identified between Hu sheep and Dorper. No DAMs were observed between distinct IMF content groups within each breed. A total of 10 lysophospholipids (LPs), including four lysophospholipid ethanolamines and six lysophospholipid cholines, were identified as the main differential precursors between Hu sheep and Dorper. Furthermore, the weighted gene coexpression network analysis uncovered three differentially coexpression modules that were significantly associated with the content of differential LPs in Dorper. From the three modules, GLB1, PLD3, LPCAT2, DGKE, ACOT7, and CH25H genes were identified as key genes regulating the metabolism of LPs. This work provides an insight into understanding the difference in flavour between different sheep breeds, as well as a basis for further exploring the regulatory mechanism of key genes on LPs.