Background. The rise in global obesity has worsened the prevalence of metabolic syndrome and related cardiovascular complications, particularly among post-menopausal women. Dysfunctions in thyroid hormone activity, critical for metabolic regulation, are often implicated in obesity and its associated conditions. This study evaluated the interactions between thyroid function, body composition, and cardiovascular health in post-menopausal women. Material and Methods. We conducted an observational, prospective, open-label clinical study, involving post-menopausal women, stratified into two groups based on weight changes after menopause: the Menopausal Weight Gain Group (MWGG) and the Menopausal Weight Maintenance Group (MWMG). We included 12 cases (MWGG) and 8 control (MWMG) women. Participants underwent cardio-metabolic assessments, including evaluations of thyroid function, blood pressure, arterial stiffness, body composition, and cardiovascular risk profiles. The statistical analysis employed t-tests and Pearson correlations. Results. The MWGG showed significant increases in both the Augmentation Index (AI@75) and adiposity markers (BMI, total fat mass, in percentage and kg, and lean–to–fat mass ratio) compared to the MWMG. A notable decrease in FT3 and the FT3/FT4 ratio was observed in the MWGG. Moreover, discrepancies in Cholesterol levels and insulinemia were reported between groups. Moreover, differences in cholesterol levels and insulinemia were reported between groups. We analyzed the correlation between blood pressure, cardiovascular stiffness, and body composition parameters; notably, there was a strong correlation between AI@75 and weight, BMI, and total fat mass, and a strong negative correlation with the lean–to–fat mass ratio. Conclusions. The MWGG presented a higher BMI, greater total fat mass (kg) and a higher percentage of total fat mass compared to the MWMG. Interestingly, we reported a significant difference in intramuscular adipose tissue between the groups. These results highlight the importance of further research to elucidate the mechanisms involved and to develop targeted interventions for managing menopause-related cardio-metabolic risks.