Frozen Teardrop is set during the Mars Century, the era that has succeeded the After Colony era, on the terraformed Mars. Since the formation of the young Mars Colony and its government, trouble has been brewing within it with the assassination of its President, Milliardo Peacecraft. In the present day, ESUN President Dorothy T. Catalonia authorizes the beginning of "Operation Mythos" to resolve the problems on Mars - which primarily involves the assassination of Relena Peacecraft.

Concurrent to the events of Mars Century are flashbacks during After Colony, told through Preventer agent Kathy Po, the daughter of Sally Po. The flashbacks detail events in After Colony leading up to the events of the series, including the origins and backgrounds of OZ Leader Treize Khushrenada and Gundam pilot Heero Yuy.