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Omics technologies enable deep profiling of human atherosclerosis but have mostly been applied in small studies lacking integration with other data modalities. AtherOMICS is a biobanking project linking multiomic atherosclerotic plaque phenotyping with blood biobanking, in vivo imaging, and clinical data. Here, we present the study protocol and show pilot results that demonstrate technical feasibility. Since August 2022, 246 patients scheduled to undergo carotid or femoral endarterectomy at Ludwig-Maximilians-Universität Klinikum (Munich, Germany), have been enrolled (median age, 73 years; 32% female), with recruitment ongoing. Plaques undergo systematic histological characterization of lipid core, calcification, intraplaque hemorrhage, fibrous cap, macrophages, and smooth muscle cells. Single-nucleus RNA sequencing (n = 17) has confirmed macrophages as the dominant intraplaque cell type, whereas paired plaque and plasma affinity-based proteomics (n = 88) quantified 2841 shared proteins showing low plaque-plasma correlation (median ρ = 0.10). Cross-modality image integration [histology, ex vivo magnetic resonance imaging (MRI), in vivo MRI, and computed tomography angiography] proved feasible. Together, AtherOMICS enables multimodal characterization of human atherosclerosis aiming for the discovery of athero-specific drug targets, molecular signatures of atheroprogression, and noninvasive biomarkers of plaque vulnerability.