Abstract Background and Aims Cardiovascular disease (CVD) and cancer share modifiable risk factors and potential molecular mechanisms. This study examines whether the American Heart Association’s Life’s Simple 7 (LS7) metric developed for cardiovascular health is also linked to mortality outcomes in cancer survivors and explores potential biological mechanisms underlying this relationship. Methods Longitudinal analyses were conducted on 779 cancer survivors from the Moli-sani study (n = 24 325), followed for 14.6 years (median). The LS7 metric includes smoking, physical activity, diet, body mass index, blood pressure, total blood cholesterol, and glucose. Each ideal metric was assigned 2 points, with scores ranging from 0 to 14. The LS7 score was categorized as poor (0–6), intermediate (7–9), and ideal (10–14) cardiovascular health. Shared biological risk factors (e.g. inflammatory and renal markers) were analysed as potential mediators. Results Cancer survivors in the ideal cardiovascular health category had a 38% lower risk of all-cause mortality compared to those with poor cardiovascular health [hazard ratio (HR) .62; 95% confidence interval (CI) .41–.94]. Similar findings were observed in cancer-free participants (HR .68; 95% CI .59–.78). Each 1-unit increase in LS7 metric was linked to lower cancer mortality (HR .90; 95% CI .82–.98). Replacing the original dietary component of the LS7 with the Mediterranean diet score resulted in reduced hazards of CVD (HR .84; 95% CI .71–1.00), cancer (HR .90; 95% CI .83–.98), and non-CVD/non-cancer mortality (e.g. deaths from neurodegenerative, cerebrovascular and respiratory diseases) (HR .83; 95% CI .70–.98). Altogether, inflammation, heart rate, and serum vitamin D accounted for over 50% of the associations between LS7 metric and mortality. Conclusions The LS7 metric, originally developed for cardiovascular health, is associated with lower all-cause and cancer mortality in cancer survivors, potentially through shared biological mechanisms. These findings support the inclusion of LS7 risk factors in public health efforts targeting both CVD and cancer outcomes.