Background: In India, an estimated 220,000 children contract tuberculosis (TB) annually, yet the absence of a gold standard test hinders effective diagnosis and reporting of childhood TB. Objective: This study aimed to analyse the clinical profile of childhood tuberculosis, utilizing relevant laboratory investigations for early diagnosis. Methods: A cross-sectional observational study was conducted at a tertiary care hospital in South India from October 2019 to October 2021. Children under 18 with tuberculosis were included. Data on demographics, symptoms, family TB history, nutritional status, and clinical findings were collected. Laboratory tests included complete blood count, ESR, Mantoux test, chest X-rays, and sputum analyses for acid-fast bacilli (AFB). Results: Among 54 children, the most common age group was over 10 years (51.3%), with a male preponderance (53.3%). Pulmonary TB was diagnosed in 44.4% of cases, while 55.5% had extrapulmonary TB, predominantly pleural (40%). Fever (60.5%) and cough (42.7%) were the most common symptoms. The Mantoux test was reactive in 40.7% of patients, particularly among the undernourished. Chest X-rays indicated TB in 93.25% of pulmonary cases, while CBNAAT showed positive results in 10 cases, with a sensitivity of 18.8% and specificity of 81.25%. Conclusions: Diagnosing childhood TB remains complex, relying on symptom evaluation, clinical history, and laboratory tests. Despite advances in diagnostic methods, negative CBNAAT results do not exclude TB, highlighting the need for thorough clinical assessment and investigation.