Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome.