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In traditional Chinese medicine (TCM), the main therapeutics is the unique TCM medicinal formula, so called Fangji, which is usually composed of multiple herbs and medical materials with integrated multiple therapeutic objects. The modern pharmacological approach to the study of Fangji, however, has been focusing on the isolation and identification of individual active components within a Fangji for cellular and molecular targets. This not only has led to the misinterpretations of mechanisms of Fangji's therapeutic actions and clinical effectiveness but also has seriously hampered the scientific research and development of TCM in general. Clearly, new omic/systematic and networking paradigms are urgently needed for deep understanding of the unique composition theories and mechanisms of effective combination therapy through TCM Fangji. In this special issue, we continued to introduce Fangjiomics-based combination therapy applications to the discovery of rational combination therapy and precision medicine.