Vascular remodelling of the uteroplacental circulation is critical for placental perfusion, fetal growth, and maternal cardiovascular adaptation. Using experimental models of immune dysregulation, including maternal C1q deficiency and regulatory T cell depletion, we demonstrate that impaired immune regulation disrupts spiral artery remodelling, uterine artery blood flow, and placental development, leading to fetal growth restriction, pregnancy loss, and—in the case of Treg deficiency—long-term cardiometabolic risk in offspring. Complementary human studies integrate advanced vascular imaging and immunophenotyping to define immune–vascular interactions in high-risk pregnancies. Ongoing preclinical therapeutic investigations aim to restore immune and/or vascular function in complicated pregnancies, including evaluation of biological therapies, vascular-targeting agents, and lifestyle-based interventions such as exercise. These findings underscore the immune–vascular interplay in pregnancy and its relevance to improving maternal and fetal outcomes.