The discovery of carbon‐based quantum dots (CQDs) has allowed opportunities for fluorescence bioimaging, tumor diagnosis and treatment, and photo‐/electro‐catalysis. Nevertheless, in the existing reviews related to the “bottom‐up” approaches, attention is mainly paid to the applications of CQDs but not the formation mechanism of CQDs, which mainly derived from the high complexities during the synthesis of CQDs. Among the various synthetic methods, using small molecules as “building blocks”, the development of a “bottom‐up” approach has promoted the structural design, modulation of the photoluminescence properties, and control of the interfacial properties of CQDs. On the other hand, many works have demonstrated the “building blocks”‐dependent properties of CQDs. In this review, from one of the most important variables, the relationships among intrinsic properties of “building blocks” and photoluminescence properties of CQDs are summarized. The topology, chirality, and free radical process are selected as descriptors for the intrinsic properties of “building blocks”. This review focuses on the induction and summary of recent research results from the “bottom‐up” process. Moreover, several empirical rules pertaining thereto are also proposed.