The World Health Organization's End TB Strategy aims to eliminate tuberculosis (TB) by 2050. Low-burden countries such as Australia are targeted for early elimination (2035), which will require an increase in the intensity and scope of case finding and treatment of people with latent TB infection (LTBI). Because 80 % of TB disease in Australia occurs in metropolitan Sydney (New South Wales) and Melbourne (Victoria), the commitment to move towards elimination has major implications for TB programs in these jurisdictions. We report on a case study analysis that compares and contrasts key attributes of each of these healthcare organizations. Such analysis has important implications for all countries seeking to implement international agreements within local health structures. Differences in the organizational structure, culture and systems of care in NSW and Victoria may facilitate or create barriers to changes in organizational system functions, especially the way in which TB prevention and LTBI treatment is delivered. Ratification of global health treaties and the development of national strategies, alone, is insufficient for realizing the promised outcomes. Even in high income countries, global health agendas such as TB elimination can be complicated by differences in local system structure and funding. As the timelines tighten towards 2035, more work must be done to identify the organizational conditions and service models that will facilitate progress towards TB elimination.