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Background Cardiovascular risk increases markedly in perimenopausal and postmenopausal women and social disadvantage can intensify barriers to prevention. In these settings, limited health literacy may further restrict women’s ability to understand cardiovascular risk, access appropriate services and translate advice into daily behaviours—potentially widening inequalities.Objectives This study investigated health literacy profiles among perimenopausal and postmenopausal women living in a socioeconomically vulnerable urban area of Florence, Italy, and examined how these profiles may guide locally tailored cardiovascular prevention strategies using the Ophelia approach.Design Cross-sectional study including hierarchical cluster analysis of Health Literacy Questionnaire (HLQ) scores.Setting Primary and community health services in a socioeconomically vulnerable neighbourhood of Florence, Italy.Participants Women aged 45–70 years attending the House of the Community ‘Le Piagge’ between October 2024 and January 2025. Of 188 recruited, 156 provided complete HLQ data and were included in the analysis.Primary and secondary outcomes Primary outcome: multidimensional health literacy profiles (nine HLQ scales). Secondary outcomes included Nutrition Literacy Instrument, adherence to the Mediterranean diet (MEDI-LITE) and Sense of Coherence.Results Four distinct health literacy profiles emerged (p<0.001). One profile (16.7%) showed broad strengths across HLQ domains, another (48.7%) combined several strengths with some more selective challenges, a smaller profile (8.3%) showed widespread challenges across domains, and a fourth profile (26.3%) showed mixed strengths and challenges together with more limited social support. Profiles characterised by more marked health literacy challenges were associated with lower education, greater financial difficulty, poorer self-rated health, lower nutrition literacy and weaker adherence to the Mediterranean diet. Among the Sense of Coherence dimensions, meaningfulness was higher in clusters with stronger health literacy profiles (p<0.001).Conclusions This study identified distinct multidimensional health literacy profiles among perimenopausal and postmenopausal women in a socioeconomically disadvantaged urban setting. These profiles provide locally relevant evidence to inform the subsequent co-design of fit-for-purpose cardiovascular prevention actions within the Ophelia framework.