Ethiopia’s commitment to achieving universal health coverage (UHC) requires an efficient and equitable health priority-setting practice. The Ministry of Health aims to institutionalize health technology assessment (HTA) to support evidence-based decision making. This commentary highlights key considerations for successful formulation, adoption, and implementation of HTA policies and practices in Ethiopia, based on a review of international evidence and published normative principles and guidelines. Stakeholder engagement, transparent policymaking, sustainable financing, workforce education, and political economy analysis and power dynamics are critical factors that need to be considered when developing a national HTA roadmap and implementation strategy. To ensure ownership and sustainability of HTA, effective stakeholder engagement and transparency are crucial. Regulatory embedding and sustainable financing ensure legitimacy and continuity of HTA production, and workforce education and training are essential for conducting and interpreting HTA. Political economy analysis helps identify opportunities and constraints for effective HTA implementation. By addressing these considerations, Ethiopia can establish a well-designed HTA system to inform evidence-based and equitable resource allocation toward achieving UHC and improving health outcomes.