Sexually transmitted infections (STIs) present significant health and economic challenges in all countries and yet are rarely prioritised for coordinated strategic attention. The 2016 World Health Assembly adopted a global health sector strategy on STIs for 2016–2021, including ambitious 2020 and 2030 goals aligned with broader sustainable development goals and targets of ending disease epidemics as public health concerns by 2030. The strategy requires actions at the country level, guided and led by governments, supported by the World Health Organization (WHO) and other partners. A number of barriers frustrate efforts to take the response to STIs to scale, including insufficient incidence data and disease surveillance, and political resistance to scientifically-proven and often cost-effective interventions and approaches. Country-level success in strategy implementation requires that WHO, Ministries of Health, and broader stakeholders look beyond the interventions required for effective STI management to also consider the broader context, processes, and politics of STIs when building and strengthening responses. Evaluating progress towards the strategy’s 2020 coverage targets and 2030 coverage and impact targets will be the key success-measurement tool, yet limiting analysis to the frame of coverage and impact targets alone will deny important opportunities to drive action and to evolve policies and programmes in dynamic contexts. Exploring and assessing the implementation context, political interest, and potential of health policies can ensure early identification of challenges and opportunities when focused on national-level policy uptake and execution. This paper applies an analytical approach to the global strategy that includes an investigation of 3 domains: process, programmatic, and political. Key questions are proposed to guide exploration of these domains to help identify and address barriers to, and leverage solutions for, policy success.