Cardiometabolic　Syndrome　(CMS)　is　associated　with　increased　risks　of　cardiovascular　disease,　type　2　diabetes　mellitus,　and　all-cause　mortality.　The　Weight-Adjusted　Waist　Circumference　Index　(WWI)　has　emerged　as　a　novel　metric　for　assessing　obesity　and　its　health　implications.　To　investigate　the　relationship　between　WWI　and　mortality　in　CMS　patients,　considering　the　mediating　role　of　inflammatory　markers.　The　study　analyzed　the　National　Health　and　Nutrition　Examination　Survey　(NHANES)　data　from　2003　to　2018　and　identified　6506　patients　with　CMS.　WWI　was　calculated　as　the　square　root　of　waist　circumference　(cm)　divided　by　weight　(kg).　Mortality　data　were　correlated　with　the　National　Death　Index　(NDI).　Cox　regression　models,　adjusted　for　demographic　and　clinical　covariates,　assessed　the　effect　of　WWI　on　all-cause　and　cause-specific　mortality.　Finally,　the　role　of　inflammatory　markers　in　the　relationship　between　WWI　and　mortality　was　explored　using　mediation　analysis.　The　study　observed　a　positive　linear　association　between　WWI　and　all-cause,　cardiovascular,　and　diabetes-related　mortalities　among　CMS　patients.　After　adjusting　for　demographic　and　clinical　confounders,　WWI　remained　a　significant　predictor　of　mortality.　Mediation　analysis　revealed　that　inflammatory　markers,　particularly　the　neutrophil　and　systemic　immune-inflammation　index　(SII),　significantly　mediated　the　relationship　between　WWI　and　all-cause　mortality.　WWI　is　an　independent　predictor　of　mortality　in　CMS　patients,　with　inflammation　potentially　linking　obesity　to　mortality　risk.　These　findings　may　inform　clinical　risk　assessment　and　management　strategies　for　CMS.