AbstractIntroductionBody mass index (BMI) fails to identify up to one‐third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity‐related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk.MethodsNational Health and Nutrition Examination Survey participants from 1999 to 2018 (N= 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC.ResultsWith metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n= 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer‐free individuals (n= 18,972). Compared with MHNW participants, MUNW participants had a 2.2‐times higher ORC risk [OR (95%CI) = 2.21 (1.27–3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46–4.42), 1.56 (0.91–2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW.ConclusionsMUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted.