Colombia has an underreporting of 30% of the total cases, according to World Health Organization (WHO) estimations. In 2016, successful tuberculosis (TB) treatment rate was 70%, and the mortality rate ranged between 3.5% and 10%. In 2015, Colombia adopted and adapted the End TB strategy and set a target of 50% reduction in incidence and mortality by 2035 compared with 2015. The aims of this study were: To evaluate whether Colombia will be able to achieve the goals of TB incidence and mortality by 2050, using the current strategies; and whether the implementation of new screening, diagnosis and TB treatment strategies will allow to achieve those WHO targets. An ecological study was conducted using TB case-notification, successful treatment and mortality rates from the last 8 years (2009-17). System dynamics analysis was performed using simulated scenarios: (1) continuation with the same trends following the trajectory of the last 8 years (Status quo) and (2) modification of the targets between 2017 through 2050, assuming the implementation of multimodal strategies to increase the screening, to improve the early diagnosis and to improve the treatment adherence. Following the current strategies, it is projected that Colombia will not achieve the End TB strategy targets. Achieving the goal of TB incidence of 10/100 000 by 2050 will only be possible by implementing combined strategies for increasing screening of people with respiratory symptoms, improving access to rapid diagnostic tests and improving treatment adherence. Therefore, it is necessary to design and implement simultaneous strategies according to the population needs and resources, in order to stride towards the End TB targets.