Even with specialist-level palliative care, cancer pain can be difficult to treat especially when the pain is complicated by profound suffering. It is paramount to consider not only the patients' biochemical factors but also their psychosocial and spiritual/existential influences. A multidimensional approach with knowledge of the risk factors for poor pain control is important to prevent, detect, and manage risk factors for intractable pain, including psychosocial distress, addictive behavior, and delirium in patients with terminal cancer. We present 3 cases of patients with advanced cancer with intractable bone pain whose hospital courses were complicated by severe psychosocial distress and delirium. We also propose an algorithm of multidimensional approach to unrelieved pain and suffering in patients with advanced cancer.