This research aims at developing adaptive medical diagnostic system driven by genetic, neural network and fuzzy logic algorithms for effective diagnosis of tuberculosis. Medical diagnosis for tuberculosis disease is a complex decision process that involves a lot of vagueness and uncertainty management, since the disease has multiple symptoms. The use of several algorithms has been explored in clinical diagnosis models for diagnosing and prescribing therapy for tuberculosis, but has challenges in transforming the vagueness and uncertainty of multiple symptoms due to the noisy nature of the disease data and over fitting of the models, this had led to the challenge of accurate classification, training, optimization, diagnosis and prescription of therapy. Object Oriented Analysis and Design (OOAD) and System Structured Analysis and Design (SSAD) methodologies were adopted in the research. The methodology involved obtaining four hundred and thirty (430) clinical data from patients with tuberculosis records at the Tuberculosis and Leprosy Hospital, Eku, Delta State. The obtained data were pre-processed using missing values imputation and numeric data encoding methods. Thereafter, a genetic algorithm was applied to the processed data to select six relevant features from the initial number of 16 features (Cough, Night sweats, Fever, Systolic Blood Pressure, Difficulty in Breathing, Loss of appetite, Sputum, Chills, Loss of pleasure, Immune Suppression, Chest Pain, Lack of concentration, Irritation, Loss of energy, Lymph Node Enlargement, Body Mass Index). The reduced dataset was split into training and test sets. The ANFIS (Adaptive Neuro-Fuzzy Inference System) was applied to perform diagnosis in which it was trained and validated on training and test sets respectively. The ANFIS was driven by Mamdani’s inference mechanism with sixty-four (64) generated rules with confidence and support scores of above 10% and 15% respectively. The developed model performance on the test sets gave an accuracy of 90% precision, sensitivity, and specificity of 100%. The results showed that all the attributes of tuberculosis contributed to the degree of the diseases based on their respective weights. Conclusively, the system accurately classified, trained attributes, and predicts the severity of tuberculosis.