The mortality rate of cardiovascular disease ranks first in the world. Its pathogenesis involves not only internal factors such as immunity, inflammation, metabolic disorders, and self-development but also external factors such as the environment. In the last decade, the emergence of single-cell technology has greatly promoted the development of disease research. Among them, the more mature single-cell RNA sequencing can carry out high-throughput analysis of single cells while studying with single-cell resolution. This technology enables people to characterize the heterogeneity of single cells, identify rare cell types in heart and blood vessels, and construct human heart cell map. With the data analysis of bioinformatics experts, it can also reconstruct the development track of the heart, to construct a map of heart development. Single-cell sequencing plays an important role in analyzing the human physiological structure and disease progression due to its advantages of single-cell resolution. The possibility of combining other omics technologies is proposed by summarizing the existing application examples and advanced technologies like spatial transcriptome. In this review, we summarize the current single-cell sequencing technologies (plate-based and droplet-based) and describe the data analysis process. The latest findings in cardiovascular disease using single-cell RNA sequencing technology are described. Finally, we discussed the shortcomings of single-cell RNA sequencing technology. At the same time, the possibility of the combination of single-cell RNA sequencing and spatial omics technology, and how to apply it to the study of cardiovascular diseases is discussed.Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.