Diagnosis of pulmonary tuberculosis (TB) is challenging in children as they often have atypical symptoms, non-specific radiological features, are paucibacillary and do not expectorate sputum. Consequently, most children undergo invasive sampling like gastric aspiration (GA) for obtaining microbiological diagnosis necessary for initiating correct treatment. We have developed an innovative, indigenous, non-invasive diagnostic workflow called SMaRT-PCR, which involves 10 minutes of Sampling with a modified Mask and TB-RNA detection with Reverse Transcriptase-PCR. Pilot study showed that the SMaRT-PCR had a 75% sensitivity and 95% specificity for paediatric TB detection. With further refinement, SMaRT-PCR can now detect TB and drug resistance simultaneously up to one week from sample collection with transport at ambient temperature. The proposed study aims to demonstrate and evaluate the clinical utility of SMaRT-PCR in a large paediatric cohort of TB suspects using a hub-and-spoke model in urban and rural settings. A total of 1200 children presenting with TB symptoms will be recruited and tested using SMaRT-PCR and standard diagnostic methods. The SMaRT-PCR’s diagnostic accuracy will be estimated based on clinical evaluation of confirmed, unconfirmed and unlikely tuberculosis. In the same cohort, we will compare SMaRT-PCR’s diagnostic accuracy with CBNAAT/TrueNAT in reference samples (sputum/GA). Furthermore, we will assess the operational adaptability of SMaRT-PCR for clinical use in diverse settings. If validated, this will be a first-of-its-kind indigenously developed technology that could potentially improve tuberculosis confirmation in multitudes of children in India and globally who rely on clinical diagnosis or undergo invasive testing for treatment.