Assisted reproductive technology (ART) has greatly benefited numerous infertile couples who would never have had their babies without this technique. However, in vitro culture is reported to cause epigenetic and transcriptomic changes on preimplantation embryos, leading to adverse effect on development, and little is known about the molecular mechanisms underlying these changes. Here, we first introduce key studies that designate the effectiveness of an omic strategy to explore the molecular mechanisms governing preimplantation development of in vitro-cultured embryos. Furthermore, we review how in vitro culture components facilitate genomic reprogramming and zygotic genome activation (ZGA) contributing to preimplantation development after somatic cell nuclear transfer (SCNT). From these different perspectives, we would search for a breakthrough to further optimize preimplantation embryo culture conditions and improve ART.