Optical imaging is unequivocally the most versatile and widely used visualisation modality in the life sciences. Yet it is significantly limited by photon scattering, which complicates imaging beyond a few hundred microns. For the past few years however, there has been an emergence of powerful new imaging methods that can offer high resolution imaging beyond the penetration limits of microscopic methods. These methods can prove essential in cancer research. Of particular importance is the development of multi-spectral opto-acoustic tomography (MSOT) that brings unprecedented optical imaging performance in visualising anatomical, physiological and molecular imaging biomarkers. Some of the attractive features of the method are the ability to offer 10-100 microns resolution through several millimetres to centimetres of tissue and real-time imaging. In parallel we have now achieved the clinical translation of targeted fluorescent probes, which opens new ways in the interventional detection of cancer in surgical and endoscopy optical molecular imaging. This talk describes current progress with methods and applications for in vivo optical, opto-acoustic and thermoacoustic imaging in cancer and outlines how new opto-acoustic and fluorescence imaging concepts are necessary for accurate and quantitative molecular investigations in tissues.