Tuberculosis (TB) is the leading cause of death from an infectious agent in the world. Most tuberculosis cases are concentrated in low- and middle-income countries. The aim of this study is to better understand tuberculosis-related knowledge about TB disease, prevention, treatment and sources of information, attitudes towards TB patients and their stigmatization and prevention, diagnosis and treatment practices in the general population of middle- and low-income countries, with a high tuberculosis burden, and provide evidence for policy development and decision-making. A systematic review of 30 studies was performed. Studies reporting on knowledge, attitudes, and practices surveys were selected for systematic review through database searching. Population knowledge about TB signs and symptoms, prevention practices, and treatment means was found inadequate. Stigmatization is frequent, and the reactions to possible diagnoses are negative. Access to health services is limited due to difficulties in transportation, distance, and economic cost. Deficiencies in knowledge and TB health-seeking practices were present regardless of the living area, gender, or country; however, it seems that there is a frequent association between less knowledge about TB and a lower socioeconomic and educational level. This study revealed gaps in knowledge, attitude, and practices in focused in middle- and low-income countries. Policymakers could take into account the evidence provided by the KAP surveys and adapt their strategies based on the identified gaps, promoting innovative approaches and empowering the communities as key stakeholders. It is necessary to develop education programs on symptoms, preventive practices, and treatment for TB, to reduce transmission and stigmatization. It becomes also necessary to provide communities with innovative healthcare solutions to reduce their barriers to access to diagnosis and treatment.