The WHO End TB Strategy aims to end the global TB epidemic by 2030, in alignment with Goal 3 of the United Nations (UN) Sustainable Development Goals (SDGs). Member States of the World Health Organization (WHO) and the UN committed to ending the TB epidemic through adoption of WHO’s End TB Strategy and the UN SDGs in 2014 and 2015, respectivel Almost half of the deaths worldwide caused by TB in 2019 occurred in the WHO South-East Asia Region, home to around a quarter of the global population. Maintaining robust progress in this Region is therefore essential if the global goal of ending the TB epidemic is to be realized. Despite substantial gains made in the Region, the threat to health worldwide posed by the COVID-19 pandemic has the potential to reverse these gains and eclipse the focus on the global TB emergency. While continuing to tackle COVID-19-related challenges, countries will need to rapidly and urgently deploy supplementary measures to address the large numbers of missed cases, poor treatment outcomes and, potentially, a higher TB burden. The Regional Strategic Plan towards Ending TB in the Region 2021–2025 clearly articulates priority interventions, analyses the challenges, bottlenecks and opportunities, and focuses on implementation considerations in the Region.