Cardiovascular disease is a result of genetic and environmental risk factors that together generate arterial and cardiac pathologies. Blood vessels connect multiple organ systems throughout the entire body allowing organs to interact via circulating messengers. Multimodality imaging achieves integration of these interfacing systems’ distinct processes, quantifying interactions that contribute to cardiovascular disease. Noninvasive multimodality imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. Multichannel multimodality imaging including optics, CT, PET and MRI, are particularly promising because they can simultaneously sample multiple biomarkers. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies.