What global grand challenges we face today that will have an impact on the homeland security landscape twenty-five years from now? Today, a grand challenge is intended as a call-to-action for a given field, to find the potential solution for a moonshot problem. Calvin Bowman, Chairman of the Urban Area Security Initiative and Senior Policy Advisor for the Mayor’s Office of Emergency Management in Baltimore City, recommends using the potential methods and organizational capacity requirements for Department of Homeland Security (DHS) science and technology (S&T) based on a focused comparison of three cases: XPRIZE, Defense Advanced Research Projects Agency (DARPA), and DHS S&T. Through a contemporary application of smart practices used by XPRIZE and DARPA, DHS can better prepare for today’s shifting technological threat environment. DHS’ current approach to grand challenges is local and linear when it should be global and innovative.