IMPORTANCE Targeted drug delivery (TDD) has potential for cost savings compared with conventional medical management (CMM). Despite positive clinical and economic evidence, TDD remains underused to treat cancer pain. OBJECTIVE To assess the cost of TDD and CMM in treating cancer-related pain. DESIGN, SETTING, AND PARTICIPANTS This retrospective economic evaluation using propensity score-matched analysis was conducted using MarketScan commercial claims data on beneficiaries receiving TDD and CMM or CMM only for cancer pain from January 1, 2009, to September 30, 2015. Participants were matched on age, sex, cancer type, comorbidity score, and pre-enrollment characteristics. Data analysis was performed from June 1 to September 30, 2017. MAIN OUTCOMES AND MEASURES Total 2-, 6-, and 12-month costs, number of health care encounters, length of hospital stay, additional components of cost, and health care utilization. RESULTS A total of 376 TDD and CMM patients (mean [SD] age, 51.88 [9.98] years; 216 [57.5%] female) and 4839 CMM only patients (mean [SD] age, 51.52 [11.16] years; 3005 [62.1%] female) were identified for study inclusion. After matching, 536 patients were included in the study: 268 patients in the TDD and CMM group and 268 in the CMM only group.