Imago is set in the future, after a nuclear war has decimated most of the earth. A foreign species, the Oankali, has made Earth a colony. The Oankali are male and female but also have a third sex, the Ooloi. Ooloi are necessary to Oankali reproduction; they lie between partners, gather and recombine genetic material, and inseminate the female to produce offspring. The main Ooloi organ, the yashi, contains genetic information about every living thing. Ooloi can cure anything with a single touch. Also, of course, an evil Ooloi could start diseases no one has ever seen before.

The Ooloi and Oankali breed with earthlings who are willing and cure them of the tumors, infertility and other effects of the war. Unwilling humans are also repaired and sent to a colony on Mars where they can live autonomously. The Oankali have little hope for these humans, as their biological aggression will eventually cause another war. The Oankali do learn one thing from the humans, cancer. While for humans the fast reproduction of cells is a dreaded disease, the Ooloi control it and use it to recreate lost limbs and repair other damage.

Imago focuses on one particular Ooloi, Judahs. He is an anomaly because he has human parents. Judahs searches for human mates, finally finding two rebels. This pair tell him of a hidden community of humans unknown to the invaders. This area too becomes a colony, but with a more human aspect.