The cellular diversity within a tumor, or intratumoral heterogeneity, correlates with poor prognosis, relapse, and patient mortality. A major factor in these outcomes may be associated with drug resistance, which is responsible for the majority of cancer patient mortalities while receiving treatments such as chemotherapy and targeted drugs. To better understand treatment-resistant populations, we are developing computational approaches to temporally measure heterogeneity and track populations longitudinally. By understanding the evolution of these complex systems, we may find new avenues to overcome treatment resistance.