Advances in high-throughput technologies to measure genome-scale changes of genes, proteins, and other biomolecular components (‘omics’) in complex biological systems have dramatically revolutionized biomedical research. However, the benefits of utilizing omics information in drug development have not yet been fully realized. Fortunately, the integration of modern systems biology efforts with traditional medicine philosophies, together with integrative bioinformatics, has driven the development of a new drug discovery paradigm. Using leukemia as a disease model, therapeutic synergism between drugs and natural products has been investigated by incorporating transcriptomics and proteomics data into a network-like understanding. Here, these recent advancements will be discussed in detail, along with perspectives in the field of drug synergism.