In-space cryogenic propulsion will play a vital role in NASA’s return to the Moon mission and future mission to Mars. The enabling of in-space cryogenic engines and cryogenic fuel depots for these future manned and robotic space exploration missions begins with the technology development of advanced cryogenic thermal-fluid management systems for the propellant transfer lines and storage system. Before single-phase liquid can flow to the engine or spacecraft receiver tank, the connecting transfer line and storage tank must first be chilled down to cryogenic temperatures. The most direct and simplest method to quench the line and the tank is to use the cold propellant itself that results in the requirement of minimizing propellant consumption during chilldown. In view of the needs stated above, a highly efficient thermal-fluid management technology must be developed to consume the minimum amount of cryogen during chilldown of a transfer line and a storage tank. In this paper, we suggest the use of the cryogenic spray for storage tank chilldown. We have successfully demonstrated its feasibility and high efficiency in a simulated space microgravity condition. In order to maximize the storage tank chilldown efficiency for the least amount of cryogen consumption, the technology adopted included cryogenic spray cooling, Teflon thin-film coating of the simulated tank surface, and spray flow pulsing. The completed flight experiments successfully demonstrated that spray cooling is the most efficient cooling method for the tank chilldown in microgravity. In microgravity, Teflon coating alone can improve the efficiency up to 72% and the efficiency can be improved up to 59% by flow pulsing alone. However, Teflon coating together with flow pulsing was found to substantially enhance the chilldown efficiency in microgravity for up to 113%.