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Background: The sustainability of palliative care services is nowadays crucial inasmuch as resources for palliative care are internationally scarce, the funding environment is competitive, and the potential population is growing. Methods: The DEMETRA study is a multicentre prospective observational study, describing the intensity of care and the related costs of palliative home care pathways. Results: 475 patients were enrolled as recipients of specialized palliative home care. The majority of recipients were cancer patients (89.4%). The mean duration of palliative care pathways was 46.6 days and mean home care intensity coefficient equal to 0.6. The average daily cost of the model with the reference variables is 96.26 euros. Factors statistically significantly associated with an increase in mean daily costs were greater dependence and extreme frailty (p < 0.05). Otherwise, a longer duration of treatment course was associated with a significant decrease in mean daily costs (p < 0.001). Conclusions: In terms of clinical and organizational management, considering the close association with the intensity and cost of the path, frailty should be systematically assessed by all facilities that potentially refer patients to home palliative care teams, and it should be carefully recorded in a standardized payment rate perspective.