Background <p>Comorbidity between depression and cardiometabolic diseases is an emerging health concern, with childhood maltreatment as a major risk factor. These conditions are also linked to unhealthy lifestyle behaviours such as physical inactivity, smoking, and alcohol intake. However, the precise degree to which lifestyle behaviours moderate the risk between childhood maltreatment and comorbid depression and cardiometabolic disease is entirely unknown.</p> Methods <p>We analysed clinical and self-reported data from four longitudinal studies (N_pooled = 181,423; mean follow-up period of 5–18&#xa0;years) to investigate the moderating effects of physical activity, smoking, and alcohol intake, on the association between retrospectively reported childhood maltreatment and i) depression, ii) cardiometabolic disease and iii) their comorbidity in older adults (mean age range of 47–66&#xa0;years). Estimates of these moderation effects were derived using multinomial logistic regressions and then meta-analysed.</p> Results <p>No meaningful moderation effects were detected for any of the lifestyle behaviours on the association between childhood maltreatment and each health outcome. Physical activity was linked to lower odds of depression (OR [95% CI] = 0.94 [0.92; 0.96]), while smoking was a risk factor for all three outcomes (OR [95% CI] = 1.16 [1.04; 1.31] or larger). Alcohol intake was associated with slightly lower odds of comorbidity (OR [95% CI] = 0.69 [0.66; 0.73]), although this association was not stable across all sensitivity analyses.</p> Conclusions <p>Lifestyle behaviours did not moderate the risk association between childhood maltreatment and depression, cardiometabolic disease, and their comorbidity in older adults. However, we confirmed that childhood maltreatment was associated with these conditions. Further research should address the limitations of this study to elucidate the most optimal targets for intervention.</p>