Clear cell carcinoma of the endometrium is a rare and aggressive histologic subtype of endometrial cancer, accounting for approximately 5–10% of cases. Despite its low incidence, it carries a poor prognosis due to its high-grade morphology, molecular heterogeneity, and resistance to conventional therapies. The disease predominantly affects postmenopausal women, with age, hormonal exposure, and genetic predispositions serving as major risk factors. Histopathologically, clear cell carcinoma of the endometrium is characterised by clear cytoplasm, nuclear atypia, and papillary or glandular patterns. At the molecular level, mutations in TP53, ARID1A, and PTEN, along with aberrations in the PI3K/AKT/mTOR pathway, are common, highlighting potential targets for therapy. Diagnosis often relies on histopathologic examination supported by immunohistochemical profiling, while emerging tools like liquid biopsy and next-generation sequencing show promise for earlier detection and personalised management. Treatment is primarily surgical, involving total hysterectomy with bilateral salpingo-oophorectomy, supplemented by adjuvant radiotherapy or chemotherapy in high-risk cases. However, conventional regimens yield limited benefit, emphasising the need for novel targeted and immunotherapeutic approaches. Ongoing research into molecular subtypes, biomarkers, and genomic profiling is shaping precision medicine strategies for improved outcomes. Despite current challenges, advances in molecular diagnostics and clinical trials offer new hope for optimising management and survival in patients with this challenging malignancy.