INTRODUCTION: The challenges related to several viral outbreaks spanning over the centuries have exceeded human resources and capacities of the health departments to deal with the consequent adversities. Each epidemic or pandemic faced has brought out the inequalities and gaps in our systems and infrastructure. OBJECTIVES: The focus of the current paper is to do a comparative study of complex challenges faced and strategies adopted by governments during the SARS, MERS, HIV, and Ebola outbreaks. METHODS: To achieve the objective, a comprehensive summary of the challenges that the world has faced, and lessons learned from the strategic management of these viral outbreaks were analysed. CONCLUSION: An inclusive approach for the development of a multi-pronged strategic framework to benefit the concerned or affected stakeholders is discussed. These actions can guide health care workers and individuals to be aware of health hazards and complexities.