The goal of precision oncology is to devise optimal treatment strategies tailored to the characteristics of the individual patient's disease. However, the widespread heterogeneity of cancer patients and drug responses pose a significant challenge in the design of effective personalized treatments. In this seminar, I will illustrate how the systematic use of integrative genomics and big-data analytics may enable physicians to provide more precise and effective personalized treatment of cancer. I will introduce a novel computational decision support platform that incorporates multi-omics and clinical data to guide precision cancer therapy. Finally, I will describe the application of our precision medicine platform to the treatment of relapsed Multiple Myeloma, an incurable malignancy of plasma cells, along with the encouraging results obtained in a pilot clinical trial at Mount Sinai.