A freehand, non-contact diffuse optical tomography (DOT) system has been developed for multimodal imaging with intraoperative cone-beam CT (CBCT) during minimally-invasive cancer surgery. The DOT system is configured for near-infrared fluorescence imaging with indocyanine green (ICG) using a collimated 780 nm laser diode and a nearinfrared CCD camera (PCO Pixelfly USB). Depending on the intended surgical application, the camera is coupled to either a rigid 10 mm diameter endoscope (Karl Storz) or a 25 mm focal length lens (Edmund Optics). A prototype flatpanel CBCT C-Arm (Siemens Healthcare) acquires low-dose 3D images with sub-mm spatial resolution. A 3D mesh is extracted from CBCT for finite-element DOT implementation in NIRFAST (Dartmouth College), with the capability for soft/hard imaging priors (e.g., segmented lymph nodes). A stereoscopic optical camera (NDI Polaris) provides real-time 6D localization of reflective spheres mounted to the laser and camera. Camera calibration combined with tracking data is used to estimate intrinsic (focal length, principal point, non-linear distortion) and extrinsic (translation, rotation) lens parameters. Source/detector boundary data is computed from the tracked laser/camera positions using radiometry models. Target registration errors (TRE) between real and projected boundary points are ∼1-2 mm for typical acquisition geometries. Pre-clinical studies using tissue phantoms are presented to characterize 3D imaging performance. This translational research system is under investigation for clinical applications in head-and-neck surgery including oral cavity tumour resection, lymph node mapping, and free-flap perforator assessment.