ABSTRACTBackgroundThe systemic inflammatory response significantly influences the progression and prognosis of various cancers. The novel Inflammatory Burden Index (IBI) was recently introduced as a biomarker to gauge systemic inflammation and evaluate cancer patient prognosis. However, studies investigating the relationship between IBI and mortality rates in cancer patients remain limited.MethodsThis study analyzed data from 2748 cancer patients enrolled in the National Health and Nutrition Examination Surveys between 1999 and 2018. We used weighted Cox regression analysis and restricted cubic spline models to examine the relationship between the IBI and mortality due to all causes, cardiovascular disease (CVD), and cancer. Furthermore, we employed Kaplan‐Meier survival curves, subgroup analyses, and receiver operating characteristic curves to elaborate on these associations.ResultsOver a median follow‐up period of 112 months, the cohort experienced 1067 deaths, including 320 from cancer, 239 attributable to heart disease, and 508 from various other causes. The Kaplan‐Meier curve indicated that individuals in the higher quartiles of the IBI faced significantly increased mortality risks compared to those in lower quartiles. Analyses using weighted Cox proportional hazards models demonstrated that subjects in the top IBI quartile were at a substantially higher risk for all‐cause mortality (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.67–2.62, p < 0.001), CVD mortality (HR = 1.95, 95% CI= 1.18–3.23, p = 0.010), and cancer mortality (HR = 2.06, 95% CI = 1.31–3.26, p = 0.002). Furthermore, stratification and interaction analyses affirmed the uniformity of these initial findings. The areas under the curve for the 3‐, 5‐, and 10‐year survival predictions for all‐cause mortality were 0.62, 0.62, and 0.67, respectively; for cardiovascular mortality, they were 0.64, 0.64, and 0.70; and for cancer mortality, they were 0.62, 0.77, and 0.70.ConclusionIn cancer patients, higher IBI levels significantly correlate with increased mortality from all causes, CVD, and cancer‐specific deaths. This index could possess considerable diagnostic and prognostic importance, possibly acting as a new biomarker for evaluating outcomes in cancer patients.