In parallel with the increasing number of oncological cases, the need for faster and more efficient diagnostic tools has also appeared. Different diagnostic approaches are available, such as radiological imaging or histological staining methods, but these do not provide adequate information regarding the resection margin, intraoperatively, or are time consuming. The purpose of this review is to summarize the current knowledge on spectrometric diagnostic modalities suitable for intraoperative use, with an emphasis on their relevance in the management of oral cancer. The literature agrees on the sensitivity, specificity, and accuracy of spectrometric diagnostic modalities, but further long-term prospective, multicentric clinical studies are needed, which may standardize the intraoperative assessment of the resection margin and the use of real-time spectroscopic approaches.