While HTA organizations employ formal and explicit processes to decide on what health technologies to prioritize for evaluations, HTA priority-setting remains a challenge due to the complex environment in which prioritization decisions are made. Currently, however, there is a lack of understanding of the complex environment, in which HTA is embedded and how particular features of HTA organizations and health systems affect HTA priority-setting. This dissertation explored how HTA organizations formally conduct HTA priority-setting and the specific role of organizational priorities, and health system policies and actors in shaping structural arrangements of HTA and conditioning HTA priority-setting. A comparative case study design was employed to examine HTA priority-setting in Canada (Alberta and Ontario) and the United Kingdom (England and Scotland) in two phases. The first phase explored the visible and intended priority-setting processes that are used in all four jurisdictions and how HTA is organized within health systems and organizations. The second phase focused on two jurisdictions, Ontario and Scotland, and identifying the dynamics and pressures arising from structural arrangements of HTA that influence HTA priority-setting. A total of 31 semi-structured key-informant interviews were conducted and analyzed along with various documents through a constructivist grounded theory approach. Findings of the study reveal that while formal and explicit processes are often employed to set HTA priorities, wider organizational priorities, and health system policies and actors can also shape HTA priorities. Dynamics arising from how HTA structurally interacts with these health system and organizational features directly and indirectly shape i) the overall allocation of HTA resource; ii) how topics are mobilized assessment; and iii) the health system policies that HTA resources serve. Overall, this dissertation shows that HTA priority-setting is far more complex - occurring in structural and tacit ways - than it is often typically considered.