A persistent challenge in developing personalized treatments for hematologic cancers is the lack of patient specific, physiologically relevant disease models to test investigational drugs in clinical trials and to select therapies in a clinical setting. Biomicrofluidic systems and organ-on-a-chip technologies have the potential to change how researchers approach the fundamental study of hematologic cancers and select clinical treatment for individual patient. Here, we review microfluidics cell-based technology with application toward studying hematologic tumor microenvironments (TMEs) for the purpose of drug discovery and clinical treatment selection. We provide an overview of state-of-the-art microfluidic systems designed to address questions related to hematologic TMEs and drug development. Given the need to develop personalized treatment platforms involving this technology, we review pharmaceutical drugs and different modes of immunotherapy for hematologic cancers, followed by key considerations for developing a physiologically relevant microfluidic companion diagnostic tool for mimicking different hematologic TMEs for testing with different drugs in clinical trials. Opportunities lie ahead for engineers to revolutionize conventional drug discovery strategies of hematologic cancers, including integrating cell-based microfluidics technology with machine learning and automation techniques, which may stimulate pharma and regulatory bodies to promote research and applications of microfluidics technology for drug development.