Cardiometabolic diseases (CMDs) are associated with increased cancer risk; however, the role of healthy lifestyle factors (LFs) in mitigating this risk remains unclear. Using data from 856 568 adults in the China Kadoorie Biobank (n = 461 047) and the UK Biobank (n = 395 521), we prospectively examined the associations of CMDs and cardiometabolic multimorbidity (CMM) with subsequent cancer risk and evaluated the potential protective effects of five low-risk LFs: no tobacco smoking, no excessive alcohol drinking, high physical activity, healthy dietary habits, and healthy body shape. We demonstrated that individuals with CMDs, especially those with multimorbidity, faced a significantly higher risk of cancer in both cohorts. Healthy LFs, particularly no tobacco smoking and high physical activity, were associated with a lower cancer risk following CMD onset. Moreover, adopting at least four healthy lifestyles could prevent an estimated 11.50%–15.30% of cancer cases among those with CMD. These findings highlight the importance of lifestyle interventions in cancer prevention, particularly for those with preexisting cardiometabolic conditions.