In this seminar I will describe methods to assess the activity of secondary metabolites within metabolomes prior to their isolation. In particular, I will discuss the development and application of new methods to perform bioactive small molecule discovery using patient-derived cell preparations containing both tumor and functional immune cells from multiple patients. These methods bypass the traditional lead discovery processes using immortalized cell lines and aim to provide lead compounds for chemo and immuno-oncology campaigns with an unprecedented depth of preclinical characterization.