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Nanoscale engineering is revolutionizing the way we prevent, detect and treat diseases. Viruses are playing a special role in these developments because they can function as prefabricated nanoparticles naturally evolved to deliver cargos to cells and tissues. My laboratory has developed a library of plant virus-based nanoparticles; through structure-function studies we are beginning to understand how to tailor these materials appropriately for biomedical applications. Through synthetic biology, we have developed virus-based delivery system carrying contrast agent and/or therapeutic cargo enabling molecular imaging and risk stratification as well as therapeutic applications targeting cancer and cardiovascular diseases. Another avenue is the development of virus-like particle platforms for cancer immunotherapy. The idea pursued is an ‘in situ vaccination’ to stimulate systemic anti-tumor immunity to treat metastases, and most importantly induce immune memory to protect patients from recurrence of the disease. In this lecture, I will highlight engineering design principles employed to synthesize the next-generation nanotherapeutics using virus-based platform technology, and I will discuss the evaluation of such in preclinical models.