The average daily gain (ADG) is a critical index for evaluating growth rates in cattle and is closely linked to the economic benefits of the cattle industry. Heredity is one of the factors affecting the daily gain of cattle. However, the molecular mechanisms regulating ADG remain incompletely understood. This study aimed to systematically unravel the molecular mechanisms underlying the divergence in ADG between high average daily gain (HADG) and low average daily gain (LADG) Angus cattle through integrated multi-omics analyses (microbiome, metabolome, and transcriptome), hypothesizing that the gut microbiota-host gene-metabolism axis is a key regulatory network driving ADG divergence. Thirty Angus cattle were classified according to their HADG and LADG. Fecal and serum samples were collected for 16S, fecal metabolome, and blood transcriptome analysis. The results showed that compared with the LADG group, the abundance of Firmicutes increased in the HADG group, while the abundance of Bacteroidetes and Proteobacteria decreased. Metabolomics and transcriptomic analysis revealed that KEGG pathways associated with differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) were enriched in bile acid metabolism. Spearman correlation analysis showed that