The pandemic of COVID-19 challenges the global health system and raises our concerns on the next waves of other emerging infectious diseases. Considering the lessons from the failure of world's pandemic warning system against COVID-19, many scientists and politicians have mentioned different strategies to improve global biodefense system, among which Sheet, Surveillance, Strategy, Salvage and Shield (5S) are frequently discussed. Nevertheless, the current focus is mainly on the optimization and management of individual strategy, and there are limited attempts to combine the five strategies as an integral global biodefense system. Sheet represents the biosafety datasheet for biohazards in natural environment and human society, which helps our deeper understanding on the geographical pattern, transmission routes and infection mechanism of pathogens. Online surveillance and prognostication network is an environmental Surveillance tool for monitoring the outbreak of pandemic diseases and alarming the risks to take emergency actions, targeting aerosols, waters, soils and animals. Strategy is policies and legislations for social distancing, lockdown and personal protective equipment to block the spread of infectious diseases in communities. Clinical measures are Salvage on patients by innovating appropriate medicines and therapies. The ultimate defensive Shield is vaccine development to protect healthy crowds from infection. Fighting against COVID-19 and other emerging infectious diseases is a long rocky journey, requiring the common endeavors of scientists and politicians from all countries around the world. 5S in global biodefense system bring a ray of light to the current darkest and future road from environmental and geographical perspectives.