Aims: Tuberculosis and Sickle cell are public health threats globally and in Nigeria. There is no study that that have captured how tuberculosis and sickle cell diseases have been managed in Nigeria. The aim of this review article is to bridge this study gap by evidently discussing the response of Nigeria and other relevant organization to these diseases and also the current challenges faced in response, management and mitigation of these diseases. This study also aims to keep the public health sector of ‘where we are’ and facilitate informed solution on ‘what can be done’ in a bid to manage these diseases more effectively. Methods: Scientific databases such as AJOL, Web of Science and PubMed were used to access relevant data on the disease of interest (Tuberculosis and Sickle cell). Articles relevant to the Nigerian setting was used and articles that did not revolve around the disease of interest were immediately excluded at first screening. Original articles not later than 2002 were included and used for this review, older articles were excluded for the purpose of this study. Results: This study revealed that the Federal Government of Nigeria showed much commitment in past years towards the fight of these diseases by setting up national programs and schemes. However, implementation has been weak since initiation. Government’s effort in time past towards mitigating these disease condition have not been effective because financial challenges of patients in getting treatments to manage these diseases. Last of all, associated comorbidities such as HIV, drug resistance and COVID-19 remain a major concern that affects response to tuberculosis and sickle cell disease. Conclusion: The government, relevant stakeholders, international and local NGOs, and ordinary individuals should must work together to effectively combat and eliminate the public health threats and concern posed by tuberculosis and sickle cell disease.