Terminally ill cancer patients often experience pain and delirium. However, opioids administered for pain management may exacerbate patients' delirium. To explore the real-world symptom trajectory associated with pharmacological interventions, including opioids and antipsychotics, in patients with cancer pain and terminal delirium. A secondary analysis of a multicenter prospective observational study. Adult patients admitted to inpatient hospice or palliative care units in Japan. Participants were eligible if they had cancer pain (Integrated Palliative care Outcome Scale: IPOS ≥2) and delirium at the time that their Palliative Performance Scale had declined to ≤20 (day 1, immediately before death). Pharmacological strategies, pain levels (using the IPOS), and delirium symptoms (using the Memorial Delirium Assessment Scale, item-9). Among a total of 1896 patients, 1396 were assessed for eligibility on day 1, and 137 met the inclusion criteria for analysis. A total of 86 (63%) patients had agitated delirium (hyperactive or mixed) with a median survival time of three days. Regarding pharmacological strategies, 32 (23%) received opioid initiation/dose escalation and 94 (69%) received regular administration of antipsychotics. These figures also included 25 (18%) patients who received both opioid initiation/dose escalation and antipsychotics. Approximately 55% of all patients had persistent cancer pain (IPOS for pain ≥2) on day 2. Among those with agitated delirium, 79% continued to exhibit agitation symptoms on day 2. Despite specialized palliative care, the combined distress of cancer pain and delirium in the last days of life remains complex and refractory.