Hypertensive disease (HTD), one of the most important risk factors for cerebrovascular and cardiovascular disorders, is characterized by high propensity to stress. Since stress is underpinned by both cardiac and neural factors, multidimensional insights are required to understand its disturbance in this disease. Here, we studied cardiodynamic, neurophysiological, and neuroanatomical signatures of stress in HTD patients and healthy controls. Subjects performed the Trier Social Stress Test, a gold-standard task comprising a baseline and a psychosocial stress period. During both stages, we measured a sensitive HRV parameter (the low frequency/high frequency [LF/HF ratio]) and online neurophysiological signatures (the heartbeat-evoked potential [HEP]). Also, we obtained neuroanatomical measures via voxel-based morphometry. Compared to controls, HTD patients exhibited increased LF/HF ratio and greater HEP modulations during baseline, reduced changes between baseline and stress periods, and non-significant stress-related HRV modulations associated with the grey matter volume of putative frontrostriatal regions. Briefly, HTD patients presented signs of stress-related autonomic imbalance, reflected in a potential basal stress overload and a lack of responsiveness to acute stress, accompanied by multimodal neural alterations. These findings extend current models of stress in HTD and inform relevant clinical and theoretical agendas targeting heart-brain interactions.