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Whereas the brain-heart axis is an emerging field in neuropsychocardiology, a central autonomic network including the insular cortex (Ic) regulates the cardiovascular system via the intrinsic cardiac nervous system. Cardiac interoception, represented in Ic, has been studied in cardiovascular diseases and inflammation. Therefore, it is important to investigate how interoception is related to cardiovascular disease in terms of its prevention and treatment. To examine the role of the Ic in cardiovascular and immune regulation, we focus on converging evidence from human stroke cohorts, lesion-symptom mapping studies, and experimental models that implicate the Ic as a causal hub within the brain-heart-immune axis. In particular, Ic plays a pivotal role in processing interoception as well as immunoception, and based on this information, Ic regulates cardiovascular and immune systems via efferent autonomic networks. Furthermore, vagally mediated neuromodulation is likely to influence interoception and immunoception and plays a pivotal role in improving cardiovascular dysregulation.