Purpose Malignancy-related hypercalcemia (MRH) is associated with a dismal prognosis. The widespread use of bisphosphonates (BPs), availability of more effective drugs in cancer treatment, and improvement in supportive care might have attenuated its impact. Patients and Methods To assess overall survival (OS) of patients with MRH in a contemporary setting, we conducted a retrospective analysis of 306 patients with solid cancer hospitalized for symptomatic hypercalcemia. A multivariable Cox proportional hazards regression model was performed to evaluate possible prognostic factors associated with MRH. Results All patients had serum ionized calcium > 5.5 mg/dL or total Ca > 10.5 mg/dL. Median age was 57 years, and the majority had squamous cell carcinoma (62%) and Eastern Cooperative Oncology Group performance status > 1 (96%). Head and neck was the most frequent primary site (28%). Forty-five percent had no previous chemotherapy (CT), and subsequent CT was administered to 32%. Eighty-three percent received BP with no survival gain. Median OS was 40 (95% CI, 33 to 47) days. Patients with a performance status > 2, altered mental status, C-reactive protein > 30 mg/L, albumin < 2.5 g/dL, or body mass index < 18 kg/m2 had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients, subsequent CT, and breast primary site. In the multivariable analysis, subsequent CT led to a median OS improvement of 144 versus 25 days (hazard ratio, 0.24; 95% CI, 0.14 to 0.40; P < .001). Conclusion In a contemporary setting, MRH remains a marker of poor prognosis. Patients treated with CT had better survival, which suggests that appropriate treatment of selected patients might alter the course of this syndrome.