The DNA, its epigenetic information and signals from the direct environment, all work together to orchestrate the development of the single fertilized oocyte into a new individual. The concept of developmental programming, attributed to the embryonic plasticity, suggests that the early life environment influences offspring characteristics in later life, but also further generations. There is increasing awareness about the use of Assisted Reproductive Technologies (ART), because, due to its high inefficiency mimicking in vivo optimal conditions, implies an extraordinary change in the environment where the beginning of a new organism takes place. Here we assessed the transgenerational effects of the cryopreserved embryo replacement on a maternal tract using the rabbit as a model. Then, one progeny derived from vitrified-transferred embryos (VT group) was compared to a cohort of animals naturally-conceived (NC group). A multi-omic approach (metabolome, proteome and epigenome) were addressed on the liver tissue in order to complete or previous phenotypic and transcriptomic characterization of F3 animals. LC-ESI-MS and LC-APCI-MS analysis were performed to interrogate the semi-polar and non-polar metabolomes, respectively. For the proteomic study, the analysis was carried on by LC-SWATH-MS. Finally, genome-wide DNA methylation profiling was studied by MBD-Seq. The healthy state was evaluated by a haematological and biochemical analysis of the peripheral blood. Targeted and untargeted metabolome analysis revealed a global metabolome alteration in the VT livers, particularly for those pathways related with the lipid metabolism. Here was detected some disturbances in the metabolism of long-chain polyunsaturated fatty acids (LC-PUFA), which was corroborated by the proteomic data. Functional analysis of the subset of proteins that differs between VT and NC livers revealed significant changes in the metabolism of the linoleic (LIN) and arachidonic (ARA) acids, whose downstream consequences directly was related with dysregulations in the growth and immune system responses. Overall results denoted that these metabolic disturbances participated in a complex network of physiological pathways that together promotes the phenotypic deviations currently observed after an embryo cryopreservation-transfer procedure (CTP). The underlying hypothesis supported by our results, is that these developmental deviations respond to changes in the epigenome, as consequence of direct perturbation of the reprogramming process by ART, which are dragged until adult life and inherited by further generations. Changes in the epigenetic suggested possible interactions between lipid and apoptotic pathways that jointly reprograms the physiology of the liver. However, based on peripheral blood parameters, the healthy status of VT animals was comparable to that of the NC group. Our data provides valuable information about the transgenerational long-term molecular effects of the embryo CTP using high-throughput sciences, which should highlight the need to study ART not only to increase pregnancy rates, but also to use ART in the safest way possible.