Lithium-rich　manganese-based　layered　oxides　(LMLOs)　are　considered　to　be　one　type　of　the　most　promising　materials　for　next-generation　cathodes　of　lithium　batteries　due　to　their　distinctive　anionic　redox　processes　contributing　ultrahigh　capacity　and　energy　density.　Unfortunately,　their　practical　applications　are　still　plagued　by　several　challenges　such　as　undesirable　interfacial　reactions　and　structural　evolution,　as　well　as　voltage　hysteresis/recession,　in　which　irreversible　anionic　redox　behavior　bears　the　brunt　as　the　primacy　factor.　Undoubtedly,　a　deep　understanding　of　anionic　redox　reaction　mechanisms　and　irreversible　behavior　of　oxygen　species　is　crucial　in　order　to　provide　essential　guidance　for　modification　strategies　for　LMLOs.　In　this　paper,　the　fundamental　understanding　of　intricate　anionic　redox　reaction　mechanisms　from　thermodynamics　models　to　kinetic　anionic　redox　reaction　pathways　is　comprehensively　reviewed,　and　the　existing　challenges　of　LMLOs　related　with　irreversible　oxygen　reaction　behavior　are　analyzed.　Furthermore,　numerous　representative　modification　strategies　for　overcoming　these　challenges,　coupled　with　their　underlying　mechanisms　for　regulating　anionic　redox　reversibility　are　summarized.　In　addition,　the　aspects　of　multi-scale　structural　modifications,　integration　of　interdisciplinary　technologies,　and　application　in　quasi-/all-solid-state　battery　systems　are　given　some　emphasis　in　terms　of　further　improvement　of　LMLOs-based　cathode　materials　for　advanced　lithium　batteries-based　energy　storage　systems.　Anionic　redox　in　lithium-rich　manganese-based　cathodes　(LMLOs)　provides　ultrahigh　capacity,　whereas　its　irreversibility　severely　plagues　LMLOs＇　applications.　A　fundamental　understanding　of　anionic　redox　reaction　mechanisms　and　origins　of　challenges　are　crucial　for　improving　the　long-term　performance　of　LMLOs.　This　review　provides　recent　progress　in　reaction　mechanisms,　challenges,　regulation　strategies,　and　perspectives　of　anionic　redox　in　LMLOs.image