Abstract Residual feed intake (RFI) describes an animal’s feed efficiency independent of the level of growth and production performance. The RFI is a commonly-used measure of feed efficiency in beef cattle. The first experiment determined differences in major ruminal bacteria and ruminal epithelium gene and protein expression between the most-efficient (M-eff) and the least-efficient (L-eff) finishing beef cattle. Results indicated that superior feed efficiency is associated with differences in bacterial species, transcriptional adaptations, and protein turnover in ruminal epithelium that might enhance energy transport and utilization. For example, M-eff group had enriched cellulose-degrading and volatile fatty acids (VFA) producing bacteria. Furthermore, M-eff cattle upregulated genes related to VFA absorption and ketogenesis in ruminal epithelium, underscoring greater energy production in M-eff cattle. Also, M-eff group had greater protein synthesis coupled with lower protein degradation in ruminal epithelium that allow efficient harvest of nutrients from less feed digested. These changes in the rumen might have helped M-eff cattle maintain similar level of growth performance while consuming less dry matter (DMI). Studies in non-ruminants have underscored a central role for maternal nutrition on offspring hindgut microbiome development. Whether this phenomenon exists in cattle is largely unknown. The objective of the second experiment was to evaluate the impact of maternal methionine supply during late-pregnancy in dairy cows on hindgut microbiome and metabolome in neonatal calves. To achieve this, Holstein heifer calves born to cows receiving either a control (CON) diet or CON plus rumen-protected methionine (MET) during the last 28 d of pregnancy were used. Hindgut microbiome was evaluated with 16s rRNA gene sequencing, whereas hindgut metabolites were measured using an untargeted LC-MS approach. Hindgut microbiome and metabolome profiles in MET heifers indicated greater capacity for the production of endogenous antibiotics and enhanced hindgut functionality and health. Those alterations could limit pathogen colonization in the hindgut while providing essential nutrients to neonatal calves at the same level of DMI. Together, such responses contribute to the ability of MET heifers to achieve better nutrient utilization to support greater growth rates during the preweaning period. These studies highlight that gut microbiome contributes, at least in part, to better feed efficiency and fetal programming in beef and dairy cattle.