Intrauterine growth retardation (IUGR) is highly prevalent in modern swine production, and many affected piglets survive past weaning and are raised for commercial pork production. This review summarizes the current understanding of the physiological challenges of IUGR piglets from a molecular perspective and evaluates recent advances in nutritional strategies aimed at mitigating their negative outcomes. Molecular approaches, including omics technologies and targeted analyses, have been employed to investigate the physiological characteristics of IUGR piglets. These approaches consistently show that IUGR piglets exhibit systemic dysfunction, including compromised gut health, increased inflammation and oxidative stress, and impaired function of multiple organs such as the intestine, liver, kidney, and immune-related tissues. Moreover, IUGR piglets often display poor muscle development and meat quality. The multifactorial nature of these issues suggests that targeting a single physiological parameter may be insufficient, and comprehensive interventions are needed to address the widespread effects of IUGR. Promising nutritional strategies such as supplementation with polyphenol-rich plant extracts, amino acids, and probiotics have demonstrated potential in improving gut integrity, beneficially modulating microbiota, and enhancing the overall health and performance of IUGR piglets. By supporting the systemic recovery of IUGR piglets, nutritional interventions could improve overall productivity in swine production systems.