The unique medical and socio-economic situation in each country affected by TB creates different epidemiological contexts, thus providing exploitable loopholes for the spread of the disease. Country-specific factors such as comorbidities, health insurance, social stigma or the rigidity of the health system complicate the management of TB and the overall outcome of each patient. First-line TB drugs are administered in a standardized manner, regardless of patient characteristics other than weight. This approach does not consider patient-specific conditions such as HIV infection, diabetes mellitus and malnutrition, which can affect the pharmacokinetics of TB drugs, their overall exposure and response to treatment. Therefore, the 'one-size-fits-all' approach is suboptimal for dealing with the underlying inter-subject variability in the pharmacokinetics of anti-TB drugs, further complicated by the recent increased dosing regimen of rifampicin strategies, calling for a patient-specific methodology. In this context, therapeutic drug monitoring (TDM), which allows personalized drug dosing based on blood drug concentrations, may be a legitimate solution to address treatment failure. This review focuses on rifampicin, a critical anti-TB drug, and examines its suitability for TDM and the socio-economic factors that may influence the implementation of TDM in clinical practice in resource-limited settings, illustrated by Tanzania, thereby contributing to the advancement of personalized TB treatment.