Vascular pathology is a contributing factor to the etiology of Alzheimer’s disease and related dementias (AD/ADRD). However, our understanding of the mechanisms causally linking cerebrovascular disease and AD/ADRD is limited. The medial temporal lobe (MTL) is a crucial brain region for memory and global cognition and is where several neurodegenerative pathologies, that reportedly interact with the vasculature, often coexist. The purpose of this narrative review is to summarize recent evidence for the interaction between vascular and AD-related proteinopathies, setting a focus on the MTL and on human pathological studies. The reviewed body of literature confirms the distinctive characteristics of the vasculature in the MTL, the high prevalence of small vessel disease pathology (i.e. arteriolosclerosis and cerebral amyloid angiopathy) in this brain region, and brings to the fore potential mechanisms causally linking vascular and AD-related pathologies (e.g. perivascular clearance, blood-brain-barrier leakage, hypoperfusion). Pinpointing the interaction between vascular and AD-related pathology in the MTL and its underlying mechanisms is important to quantify the effects of vascular pathologies on the development of AD/ADRD and to assess the effectiveness of therapeutics that directly or indirectly target vascular dysfunction.