From the Cradle is set centuries in the future, in a time when many of the galaxy's species are just reaching out into the stars. Much of the galaxy remains unexplored by anything besides telescopes, and the development of the jump gates which allow faster-than-light travel between locations is largely stalled by the limitations of technology and by the lack of conduits large enough to get a starship through. As such, the galactic empires that try to claim the galaxy for themselves find themselves stalled, left to consolidate the systems already linked.

There are dozens of species scattered about this part of the galaxy, but there are four major powers: the aquatic Twis'rin and Captab, the immense Balorim, and the secretive Doggei, each with their own slices of the galaxy and their own growing menagerie of allies and supplicants. Each of these constantly search for an advantage over their rivals, going so far as to pull other species into space and hoping to influence them. Thus, the humans, granted interstellar technology by the Captab and the Balorim. This technology allowed them to found their first interstellar colony on Epsilon Indi III, now known as Persephone.

The colony is popular, having attracted a quarter-million colonists, but still poor, as most industries are young and reliant on heavy imports and subsidies from Earth. Ambassadors and foreign traders, lured by access to Earth's resources and Persephone's status as the only human planet to allow alien visitors, crowd the colony, rubbing shoulders in cramped quarters with impoverished travellers and career criminals looking for opportunities of their own. And though the tension of Persephone, the tensions of the galaxy rage, threatening to capture the fledgling colony in their centre.