The lack of quantitative information during surgical guidance is still nowadays a major unmet need. The aim of this thesis project is to develop innovative, real-time multi-modal optical imaging techniques for open and minimally invasive surgical guidance, by providing quantitative information on fundamental physiological parameters of a certain tissue, such as oxygen saturation. This work is largely built on Spatial Frequency Domain Imaging (SFDI) and Single Snapshot Imaging of Optical Properties (SSOP). An endoscopic imaging system based on SSOP was implemented and validated on tissue mimicking phantoms and then further developed into an handheld version adapted for pre-clinical trials. A multi-modal referencing platform was also develope...