Genitourinary syndrome of menopause (GSM) has traditionally been framed as a consequence of estrogen- deficiency-related vulvovaginal atrophy, yet contemporary evidence indicates a broader disorder spanning epithelial, stromal, microbial, vascular, neural, sexual, and lower urinary tract domains. This systematic literature review synthesized recent evidence to determine how biological and clinical phenotypes relate to treatment response and to assess the basis for phenotype-informed management. Scopus was searched using terms for GSM or vulvovaginal atrophy, menopause, major hormonal, non-hormonal, and energy- based interventions, and clinical outcomes. Of 771 records identified, 420 records published before 2022 were removed. After article-type, language, and scope screening, 43 primary studies were included in the qualitative synthesis. Evidence was organized into four themes: biological architecture and objective phenotypes; clinical phenotypes and multidomain burden; differential therapeutic responses; and patient- specific determinants of management. The synthesis indicates that GSM is not adequately represented by epithelial thinning alone. Vaginal tissue remodeling, collagen architecture, microbiome composition, microvascular and neural characteristics, and emerging molecular markers coexist with heterogeneous genital, sexual, and urinary manifestations. Therapeutic responses were similarly domain-specific: hormonal, non-hormonal, and energy-based approaches differed in the outcomes measured, biological targets, evidence maturity, durability, and relevance to particular patient groups. Local estrogen remains supported by a comparatively mature evidence base, whereas energy-based and regenerative strategies show biological and clinical signals but greater heterogeneity and uncertainty. Breast-cancer survivors and women receiving endocrine therapy exemplify the need to integrate safety constraints with symptom priorities and treatment preferences. Overall, contemporary GSM evidence supports a mechanism- phenotype-intervention-outcome framework rather than a uniform treatment hierarchy. Standardized phenotyping, core outcome sets, longer comparative trials, and explicit incorporation of patient preferences are required before phenotype-guided treatment can be validated as a clinical algorithm.