"Kissdum R: Meguriahi" is a science fiction anime series set in a future where humanity faces an existential threat from mysterious alien creatures known as the Hadeans. These beings emerge from a dimensional rift and begin attacking Earth, decimating human populations and leaving devastation in their wake. The story primarily revolves around Neneko Isaki, a young woman who becomes a key figure in humanity's struggle for survival after she is revealed to possess a unique ability to control the Hadeans. Her power, known as the "Kissdum," becomes a focal point for both human and alien forces.

The narrative follows Neneko as she joins the military organization ENG, which is tasked with combating the Hadean threat. ENG deploys advanced mecha units called "Engels" to fight the aliens, and Neneko becomes a pilot of one such unit. Her journey is intertwined with that of Shuu Aiba, a skilled Engel pilot and her childhood friend, who harbors deep feelings for her. Their relationship evolves amidst the chaos of war, adding emotional depth to the story.

As the series progresses, the origins of the Hadeans and the true nature of the Kissdum are gradually revealed. The Hadeans are not merely mindless invaders but are connected to a larger, more complex inter-dimensional conflict. Neneko's role as the Kissdum wielder becomes increasingly significant, as her powers hold the key to understanding and potentially ending the war. The series explores themes of sacrifice, loyalty, and the blurred lines between humanity and monstrosity, as characters grapple with their roles in a seemingly endless conflict.

The plot is driven by intense battles, political intrigue, and personal struggles, with the fate of humanity hanging in the balance. The series balances action-packed sequences with moments of introspection, delving into the psychological toll of war on its characters. Neneko's growth as a protagonist, alongside the development of supporting characters like Shuu and other members of ENG, adds layers to the narrative, making it a compelling exploration of survival and resilience in the face of overwhelming odds.