Sexual health is multidimensional across the lifespan. At midlife, women may face challenges to sexuality, often requiring intervention. Menopause-related and age-related hormonal changes intermingle with common medical conditions and contribute to biological substrates less favorable to a healthy sexual response. Psychological, sociocultural, and relational factors modulate the impact of such changes positively or negatively, contributing to adaptation or manifestation of sexually related distress. A comprehensive diagnostic approach and multidimensional management are needed to address sexual symptoms due to both menopause and aging, individualizing non-pharmacological and pharmacological evidence-based treatment options according to personal goals and expectations in the woman/couple.