<p>The intricate processes of feto–placental development are regulated by both genetics and the nutritional environment. The placenta mediates nutrient transfer to the fetus and waste transfer to the maternal circulation to facilitate proper fetal cell fate specification. Disruptions in these fate-regulatory programmes can lead to maternal and fetal complications. We explore how metabolic–epigenetic mechanisms programme feto–placental development, discussing the roles of metabolic sensing mechanisms. This Review covers the roles of nutrient metabolite-dependent protein modifications, lipid signalling, steroid signalling and oxygen signalling in regulating particular phases and lineages of feto–placental development. Understanding these environmental–genetic interactions is crucial for elucidating the limits of developmental plasticity, the pathogenesis of pregnancy-related disorders and the potential therapeutic windows we can leverage to improve maternal and fetal outcomes.</p>