Ischemia with no obstructive coronary artery disease (INOCA), often due to coronary microvascular dysfunction (CMD), disproportionately affects women and may be linked to cognitive impairment and increased risk of dementia. While CMD and cerebral small vessel disease (CSVD) share similar risk factors and may contribute to cognitive decline, the mechanistic pathways connecting these conditions in women remain unclear. We conducted a cross-sectional observational study with a planned enrollment of 100 women aged 18 years and older with symptoms of INOCA and suspected CMD, recruited from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation–Pre-Heart Failure with Preserved Ejection Fraction study (ClinicalTrials.gov identifier: NCT03876223) and the Microvascular Aging and Eicosanoids–Women’s Evaluation of Systemic Aging Tenacity (MAE-WEST) (“You are never too old to become younger!”) Specialized Center for Research Excellence (SCORE) (U54AG065141) studies at Cedars–Sinai Medical Center and the University of Florida. Each participant underwent a comprehensive assessment protocol, including advanced brain magnetic resonance imaging to quantify markers of CSVD, cardiac MRI to evaluate CMD, non-mydriatic retinal imaging, peripheral vascular function testing, and an extensive battery of cognitive assessments. Clinical, sociodemographic, and vascular risk factor data were collected. We analyzed cross-sectional associations between multimodal imaging biomarkers and cognitive performance. This protocol describes the first multidimensional, imaging-based investigation to integrate assessments of CMD, CSVD, retinal microvasculature, and cognitive function in women at risk for INOCA. Findings will enhance our understanding of the shared vascular mechanisms underlying cognitive decline and inform strategies for early intervention in at-risk women.