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This paper presents a mathematical model aimed at studying the global behaviour and optimal control strategies for Typhoid fever. The primary objective of this study is to identify the most effective control strategy that minimizes the spread of the disease. To achieve this, we calculate the effective and basic reproduction numbers and utilize them to investigate the existence and stability of the equilibria. Furthermore, we investigate the global impact of each model parameter on the variables using Latin Hypercube Sampling and Partial Rank Correlation Coefficient. The necessary conditions of the optimal control problem are analyzed using Pontryagin’s maximum principle, and the numerical values of the model parameters are estimated using the maximum likelihood estimator. The results indicate that the optimal use of vaccination for susceptible individuals, as well as the screening and treatment of asymptomatic infected individuals, have a significant impact on reducing the spread of the disease in endemic regions.