PURPOSE We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.