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Background/Objectives: Endometrial cancer (EC) is a multifactorial disease influenced by metabolic, hormonal, and environmental factors. Trace and macroelements play a critical role in cellular homeostasis, oxidative stress, and tumor progression; however, their relationship with EC grading and clinical characteristics remains insufficiently understood. Methods: This study evaluated the concentrations of selected macro- and trace elements (Na, K, Ca, P, Mg, Mn, Cu, Zn, Be, As, Cr, Mo, Ti, Tl, Pb) in patients with endometrial cancer (G1–G3) and a control group (C). Elemental analysis was performed using inductively coupled plasma optical emission spectrometry (ICP-OES). Associations between elemental concentrations and clinicopathological variables, including age, body mass index (BMI), menopausal status, diabetes, and smoking, were assessed using appropriate statistical tests, including ANOVA with Tukey’s post hoc analysis and Student’s t-test. Multivariate regression analysis was performed to identify independent predictors of elemental alterations. Results: Significant differences in elemental concentrations were observed across EC grading. Higher-grade tumors were associated with increased levels of Ca, P, Mg, and Mn, while Na and K showed a decreasing trend with tumor progression. No statistically significant differences were observed for Zn, Ti, Tl, or Pb across histological grades. Stratified analyses demonstrated that clinical and metabolic factors had a limited and selective impact on elemental profiles. Age and BMI were associated with minor variations in selected elements, whereas menopausal status, diabetes, and smoking showed predominantly non-significant or inconsistent effects. Multivariate analysis identified histological grade as the primary determinant of elemental alterations, while other variables exhibited weaker or element-specific associations. Conclusions: Elemental homeostasis in endometrial cancer is primarily associated with tumor progression rather than systemic metabolic or lifestyle factors. Changes in Ca-, P-, Mg-, and Mn-related pathways may reflect tumor-driven metabolic reprogramming, whereas most trace elements remain relatively stable. These findings suggest that elemental profiling may provide insight into EC biology, although its clinical utility requires further investigation.