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Macrophages play a central role in atherosclerosis by internalizing modified lipids and transforming them into foam cells, thereby driving plaque formation and progression. Mitochondrial metabolism is critically involved in regulating macrophage function, and targeting mitochondrial dysfunction may provide strategies for limiting plaque inflammation and improving plaque stability. Advances in high\u2010throughput omics technologies and bioinformatic analysis methods have provided powerful tools for in\u2010depth investigation of mitochondrial function. This review first summarizes macrophage heterogeneity and foam cell formation in atherosclerotic plaques. It then compares mitochondrial omics approaches, including proteomics, interactomics, metabolomics, lipidomics, isotope tracing, and emerging single\u2010cell and spatial omics strategies. Finally, it discusses how mitochondrial dysfunction and metabolic reprogramming contribute to macrophage foam cell formation, plaque inflammation, and atherosclerosis progression.<\/jats:p>","DOI":"10.1002\/pmic.70172","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T14:36:30Z","timestamp":1786804590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Omics in Macrophage Foam Cell Formation and Atherosclerosis"],"prefix":"10.1002","author":[{"given":"Enhui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  Shanghai China"},{"name":"Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"2350","article-title":"Global Burden of Cardiovascular Diseases and Risks Collaborators","volume":"82","author":"Mensah G. 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