Cancer prognosis and treatment efficacy are assessed by evaluating the hallmarks of a tumor which are volume change of the tumor and the vascular network reformation around a tumor. Non-invasive quantitative assessment of those indications, in-vivo, is still a challenge for traditional imaging modalities, owing to a large interrogation area and deep-seated molecular (fluorescence) signal in highly scattering, anatomically complex skin tissue. Currently available techniques either utilize surgically implanted imaging windows or conduct terminal experiments for each time point. The former is prone to inflammation at the implantation site thus interfering with the tumor microenvironment. The latter one is prone to sample variability thus results in a pseudo-longitudinal outcome for tumor development. Here, we combine Intravital Fluorescence Tomography (IFT) and Spectral Domain Optical Coherence Tomography (SD-OCT) for tumor imaging with a Non-invasive Intravital Imaging Window (NIIW) for tissue stabilization. This platform enabled us to follow tumor development non-invasively covering tumor initiation, development and regression on the same animal over months-long period. IFT-OCT multimodal imaging not only reveals tumor volume change but also skin anatomical features, and it is capable of revealing neo-vascularization around the tumor site. This platform thus serves as a useful non-invasive tool to explore future research questions pertaining to cancer biology in common fluorescence-based mouse models, such as tumor progression or treatment efficacy. In addition, our multi-modal platform alleviates the burden put on animals while imaging and reduce the experimental cost significantly.