Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing (B = 0.1, P ≤ 0.001), more recent surgery (B = -0.2, P ≤ 0.05), outpatient opioid use (B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis (B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing (B = 1.6, P ≤ 0.05), higher anxiety (B = 3.7, P ≤ 0.05), lower depression (B = -4.9, P ≤ 0.05), metastatic disease (B = 16.2, P ≤ 0.05), and outpatient opioid use (B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions.