To systematically investigate the metabolic and microbial differences in feed efficiency between Hereford × Simmental (H × S) crossbred and purebred Simmental cattle (S × S), 20 steers (initial weight = 268.80 ± 30.88 kg; initial age = 273.00 ± 14.09 days) were used, which were housed in mixed pens and fed a low-energy diet (0.75 Mcal Neg/kg DM). This study revealed that the level of Hypoglycin B was related to a reduced T3, which could affect growth performance. Metabolomics analysis identified Hypoglycin B, lysoPC, and DHAP as key discriminative metabolites. Pathway enrichment analysis revealed that these metabolites were primarily mapped to glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; and pantothenate and CoA biosynthesis. In our study, the relative abundances of Succinivibrio and Clostridium_sensu_stricto_6 were significantly greater in the H × S group than in the S × S group; it may have stronger energy extraction abilities and matches their lower F/G. Romboutsia was positively correlated with Hypoglycin B and negatively correlated with LysoPC (20:2 (11Z,14Z)/0:0), which might be related to changes in blood metabolites. Nevertheless, these explanations remain correlational and require functional validation through targeted interventions.