Varying associations are reported between Five‐Factor Model (FFM) personality traits and cardiovascular disease risk. Here, we further examine dispositional correlates of cardiometabolic risk within a hierarchical model of personality that proposes higher‐order traits of Stability (shared variance of Agreeableness, Conscientiousness, inverse Neuroticism) and Plasticity (Extraversion, Openness), and we test hypothesized mediation via biological and behavioral factors. In an observational study of 856 community volunteers aged 30–54 years (46% male, 86% Caucasian), latent variable FFM traits (using multiple‐informant reports) and aggregated cardiometabolic risk (indicators: insulin resistance, dyslipidemia, blood pressure, adiposity) were estimated using confirmatory factor analysis (CFA). The cardiometabolic factor was regressed on each personality factor or higher‐order trait. Cross‐sectional indirect effects via systemic inflammation, cardiac autonomic control, and physical activity were tested. CFA models confirmed the Stability “meta‐trait,” but not Plasticity. Lower Stability was associated with heightened cardiometabolic risk. This association was accounted for by inflammation, autonomic function, and physical activity. Among FFM traits, only Openness was associated with risk over and above Stability, and, unlike Stability, this relationship was unexplained by the intervening variables. A Stability meta‐trait covaries with midlife cardiometabolic risk, and this association is accounted for by three candidate biological and behavioral factors.