Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, which affects multiple organs concomitantly. Cardiac amyloidosis is, however, the major cause of morbidity and mortality in this population due to infiltrative/restrictive cardiomyopathy. The two most common forms of cardiac amyloidosis are immunoglobulin light-chain (AL) and transthyretin amyloidosis (ATTR). Whereas cardiac involvement determines the prognosis in both AL and ATTR, vascular involvement is common and may contribute to the impaired cardiovascular profile in these patients. Several works in the literature suggest that the vascular mechanisms that control circulatory function are impaired in patients with ATTR. Here, we provide an overview of the pathophysiological mechanisms involved in vascular dysfunction in patients with ATTR. We also discuss the complex interplay of these mechanisms, including characteristics of the haemodynamic profile of heart vessels and pulmonary and peripheral arteries. Vascular dysfunction features, including stiffness and endothelium-dependent vasodilation, are discussed along with the impact of regulation of systemic ATTR on microcirculation blood flow. The specific role of the metaboreflex is also depicted. Finally, we discuss the potential clinical impact of therapies on vascular dysfunction associated with systemic ATTR. A specific focus is made on the beneficial effect of training in patients with systemic ATTR. Overall, this review aims to highlight the critical role of vascular dysfunction in patients with systemic ATTR.