As global aging accelerates, frailty and depressive symptoms have emerged as critical contributors to cardiovascular disease (CVD) risk among older adults. However, the dynamic interplay between these factors remains underexplored. Here, we examine the associations among frailty, depressive symptoms, and incident CVD using data from five international cohorts (HRS, CHARLS, SHARE, ELSA, MHAS) involving individuals aged 50 and above. Our findings reveal that frailty significantly increases CVD risk, with depressive symptoms partially mediating this relationship. Transitions into frailty elevate CVD risk, while improvements reduce it. Cross-lagged panel network analysis identifies consistent CVD predictors, including hypertension, diabetes, and mobility issues. Subgroups with stronger associations include frail males, older individuals, working or retired people, and those with unhealthy lifestyles. These results underscore the need for integrated interventions targeting frailty and depressive symptoms to prevent CVD in aging populations.