Aortic aneurysm (AA) and atherosclerosis (AS) are characterized by ambiguous comorbid relationships between them. This review discusses the molecular mechanisms of the development of these pathologies caused by heterogeneity, plasticity, intercellular interactions, embryonic origin, and regional specificity of arterial cells revealed using single-cell transcriptomics approach in humans and in animal models. The importance of interplay between genetic and environmental factors determining functional state of the vessels and development of pathology through dynamic changes in the arterial cellular composition within the ontogenetically regulated spatiotemporal continuum is emphasized, which creates conditions for the development of comorbidity between the diseases. Understanding the key molecular mechanisms underlying the comorbidity of AA and AS is important for the development of new therapeutic strategies for these pathological conditions.