Background: For physicians and patients, survival estimation is vital for the treatment plan, especially with frequent use of new therapeutic agents in metastatic breast cancer (MBC). The Chuang’s Prognostic Scale (CPS) is a validated prognostic score that may be useful in the avoidance of unnecessary palliative systemic treatment. Aim: The present study aimed to evaluate the CPS in survival prediction in patients with MBC after at least two lines of palliative systemic chemotherapy protocols (PSCPs). Methods: CPS was prospectively measured in 221 patients with MBC. The total score ranged from 0 to 8.5; the lower score refers to a good prognosis. The survival assessment was made by the Kaplan–Meier curve and the survival difference among the groups was estimated by log-rank test. Results: Using the cutoff value of CPS 5.7, the patients were classified into two groups: Group A had score ≤5.7 (174 patients, 78.7%) and Group B had CPS score >5.7 (47 patients, 21.3%). About 86.2% of the patients in Group A survived >3 months (median survival was 165 days, 95% confidence interval [CI]: 77–261) compared with 21.3% of patients survived in Group B (median survival was 81 days, 95% CI: 55–123) (P = 0.00). The sensitivity, specificity, positive predictive value, and negative predictive value were 97.6% (95% CI: 87.4–99.9), 98.3% (95% CI: 95.2–99.7), 93.2% (95% CI: 81.6–97.7), and 99.4% (95% CI: 96.2–99.9), respectively, for the 3-month mortality prediction. Conclusion: CPS could be helpful in estimating the survival outcome in patients with MBC who received at least two PSCPs.