Precision medicine represents a new era of healthcare where therapies are personalized and tailored based on the molecular underpinnings of diseases. Scientific breakthroughs in genomics and molecular profiling techniques and the advent of novel targeted biotherapies have synergized and enabled wide clinical adoption of precision medicine and its vision. Yet, to help unlock the full potential of precision medicine, current clinical frameworks that are designed for a traditional, “one-size-fits-all” approach to patient care will need to evolve to address the unique features of this novel treatment paradigm. Furthermore, given that many of the emerging targeted therapies – such as engineered cell-based therapies or “living drugs” – are based on complex biology and are early in their clinical development and translation, there are remaining questions around successfully predicting and monitoring their therapeutic efficacy and responding appropriately to potential signs of toxicities. Therefore, to make precision medicine effective and broadly applied in clinical practice, we need tools that can 1) help us accurately predict and monitor therapeutic responses and 2) allow for precise control of emerging cellular therapeutic approaches to regulate their activity and thereby prevent or mitigate potential toxicities. This dissertation details the use of imaging strategies and a new chemical biology tool to address the abovementioned shortcomings in modern precision medicine. These strategies can be used both independently and in a complementary manner. The first half of the thesis outlines the use of molecular imaging as biomarkers to characterize the biological target of interest and to monitor responses to therapy in settings of solid tumor and bacterial infection. The second half describes the development and evaluation of a small molecule-based platform that can be used to selectively regulate a broad category of proteins as well as next-generation cellular therapies. Together, the proposed biomarker imaging and regulation strategy may serve as powerful, complementary approaches that can be used to not only guide therapy selection but also to monitor and regulate them as needed, helping to push the boundaries of precision medicine.