*The series centers on Zim, a member of the extraterrestrial Irken species and the Irken Empire from the planet Irk. The empire's goal is universal conquest and has a social hierarchy based solely on physical height. The empire's leader is called The Almighty Tallest; at the beginning of the series the position is jointly held by two equally tall individuals. Zim is an outcast; he is delusional, very short, overzealous, narcissistic, and megalomaniacal.

After a six-month journey across the universe, Zim arrives at the "mystery planet" which turns out to be a dark, dystopian, and satirical version of Earth centuries into the future, with rampant mindless consumerism, although it appears that humans have abolished all wars.

A delighted Zim quickly goes to work and sets up his base in a random suburb; The Tallest are dismayed by his success. A short-statured Zim disguises himself as a human child with a green complexion (which he claims is caused by a "skin condition"). The show follows his attempts to conduct espionage by attending a local school (spelled "Skool") and planning to conquer and enslave the world at his base.

Opposing Zim is his classmate Dib, a paranoid young boy who is obsessed with the paranormal and supernatural and the only human (besides his sister) who sees through Zim's disguise. Dib is determined to expose and thwart Zim, despite the hostility and mockery he receives from his oblivious peers for doing so.

Supporting characters include Dib's cynical and apathetic sister Gaz ; Zim and Dib's demonic teacher Ms. Bitters; and Dib and Gaz's famous, but neglectful father Professor Membrane. Later in the series, other alien characters begin to appear, including Tak, a fellow Irken seeking revenge against Zim; Lard Nar, the leader of a resistance group called The Resisty who wants to overthrow the Irken Empire; and Sizz-Lorr, Zim's former employer from Foodcourtia who attempts to recapture him.*