The systematical associations between stroke and coronary heart disease (CHD) remain controversial and uncertain. Network construction and modularized analysis have become powerful tools in the field of systems biology research, which can help us to mine the multidimensional characters of correlation between the two diseases in depth. A total of 218 stroke-related and 204 CHD-related genes were identified via the Online Mendelian Inheritance in Man database; text searching engine (Agilent Literature Search 2.71) and MCODE software were employed for network construction and module division, respectively. Finally, 67, 21, 7, and 196 overlapping genes, hubs, modules and modular functions were identified between stroke and CHD, respectively. The overlapping genes, which should be responsible for the similar phenotypes, highlighted the molecular signatures of the two linked diseases. Additionally, the analysis of modules and their functional annotations showed potential dependent and independent risk factors, such as atherosclerosis, cholesterol homeostasis, plasma lipoprotein particle remodeling and response to oxidative stress, etc. Moreover, the potential mechanisms by which the same biological process activating pathological cascade or risk component-based shared pathway between stroke and CHD were uncovered, which may provide useful insights for further drug development and cost saving.