Abstract: The properties of traditional Chinese medicines (TCM) include five main aspects: four Qi, five flavors, ascending and descending, floating and sinking, and channel tropism and toxicity. Through processing, the properties can be enhanced, moderated, or altered to satisfy different clinical needs. Previous analyses of changes in the properties of traditional Chinese medicine caused by processing have mostly been based on traditional Chinese medicine theory; limited research has examined these changes using modern scientific methods. Using "traditional Chinese medicine processing chemical biology" as a guide, a strategy of "target identification-ligand fishing" is used to establish a chemical biology-driven platform to study the chemical basis, and direct target and molecular mechanism of differences in efficacy of traditional Chinese medicines caused by processing, so as to reveal the scientific connotation of the changes in the properties of traditional Chinese medicine processing. It would provide guidance to enrich processing theory, decipher the processing technique, develop the industry, and also to provide strong support to optimize the processing technology, establish decoction pieces quality standards, and ensure clinical efficacy. Ultimately, it helps to expand the paradigm of traditional Chinese medicine processing research in the new era.