According to more and more severe situation of clinical blood shortage and blood shortage in many urban medical institutions in China, the research on the influencing factors of blood shortage and its architecture is put forward. Based on the Interpretative Structure Model (ISM), a hierarchical digraph of impact factors with a certain logical relationship is established to analyze the influencing levels of each factor on blood shortage. The results show that the influencing factors of blood shortage are divided into six layers and four levels such as shallow level, middle level, deep level and the deepest level. The low blood donation rate and its driving factors are the main factors leading to the emergence of blood shortage. Low blood donation rates are affected by a range of deep and the deepest factors. To fundamentally solve the dilemma of blood shortage, the focus is on increasing the rate of unpaid blood donation, which requires the establishment of a series of long term mechanisms for blood donation and recruitment. Therefore, a more fair, complete, smooth and transparent blood security system and social environment should be created.