The series explores some folk religion themes such as possession, exorcism, shamanism, yūrei, and yōkai.

The manga setup is scenario-to-scenario, with many plots intertwining classic Japanese culture and modern day realities, with occasional references to Western influences.

While the overarching storyline focuses on Reiko's contention with her arch-nemesis, Astaroth, the series is mostly character-driven and serves to gradually develop characters, especially the main protagonists.

Mitsuhide provides Mikami with a spear tipped with a Seirei Seki (精霊石, "Spirit Stone") with which to kill Nosferatu who is protected by his loyal servant Ranmaru Mori — a demon who can take the shape of a white spider.

Nosferatu captures Mikami's associates, Emi Ogasawara, Doctor Chaos and Maria and begins to drain their blood.

Released in 1993 for the Super Famicom, Natsume's Ghost Sweeper Mikami: Joreishi wa Nice Body (ゴーストスイーパー GS美神 〜除霊師はナイスバディ〜, Gōsuto Suīpā GS Mikami 〜Joreishi wa Naisu Badi〜) is a side-scrolling platform game where the player controls Reiko through multiple stages.

In 1993, Ghost Sweeper Mikami, along with Yaiba, received the 38th Shogakukan Manga Award for the shōnen category.