Full Text Article. Also available at http://article.sapub.org/10.5923.j.am.20190903.02.htmlThis paper concentrates on the mathematical model for optimal control and cost-effectiveness analysis of tomato yellow leaf curl virus disease. The boundedness of the model has been analytically examined. The preferable optimal level of the intervention strategy to reduce the spreads and the cost of implementing control strategies were determined by introducing the time-dependent control. Pontryagin’s maximum principle was used to determine necessary conditions for the optimal control of the disease while numerical results obtained through forward-backward sweep method and fourth-order Runge-Kutta scheme using the forward solution of the state equations. The cost-effectiveness analysis results show that protective netting and removal of the infected plant is the most cost-effective strategy to combat the epidemic of tomato disease with limited resources. Therefore, TYLCV can be controlled if the farmers will effectively apply protective netting and remove the infected plants from the farm.