Preterm birth (PTB) is the single-most important determinant of infant adverse outcome worldwide, accounting for over 1 million neonatal deaths a year. Given its complex pathophysiology, prediction and prevention of PTB remain elusive. Current screening methods lack accuracy and reliability, and have failed to reduce the incidence and consequences of PTB. Hence, there remains a real need to develop noninvasive and more cost-effective screening tests, which can facilitate earlier identification of women at greatest risk, more timely prevention, and better risk stratification and management of PTB. Spectroscopic techniques have shown great promise to meet this demand. Therefore, in this article, the literature is reviewed to assess current evidence regarding the potential application of spectroscopic techniques to predict PTB via in vitro analysis of biofluids as well as in vivo study of cervical remodeling. In addition, preliminary data exploring the use of Raman spectroscopy (RS) to analyze cervicovaginal fluid (CVF) in pregnancy as a predictive tool for PTB is detailed for the first time with the aim to inform future avenues of research.