Aegis of Earth: Protonovus Assault is set 50 years after the "Silent Apocalypse", a catastrophic event that brought monsters to the world, driven solely by their desire to kill humans. These creatures have gathered in a few remaining cities powered by the new element altenite.
In its core, this game is a tower defense game: monsters attack the city in waves, and are shot down by defense machines bought by the player. The cities are constructed as rings, with each ring offering unique defensive capabilities. During battles, these rings can be rotated individually to meet the requirements of the current attack. When multiple weapons from different rings are perfectly aligned, they form a more powerful weapon.
Between attacks, there is an unlimited planning phase in which the player develops their city: besides buying new weapons and upgrades, they must also manage structures for refugees and research advanced weaponry. As the game progresses, the player will take control of multiple cities, allowing them to jump between locations using a world map.
The frame story is told through dialogues between anime characters, who are also present during battles and may trigger their special abilities. However, the player has no direct influence over which ability is activated, as it depends on the character's focus level. The player can keep their focus high by thanking team members after a mission.