The City is actually a structure that began on Earth. The mechanical beings known as Builders, which move around reforming and creating new landscapes, appear to have begun building without end, creating an enormous structure with little internal logic or coherence. There exists some kind of major isolation system between the gargantuan floors of The City. Between them, there are entire layers of an unknown, nearly-indestructible material called "the megastructure". Attempts to approach the megastructure result in a massive safeguard response so as to prevent trespassing. Bypassing the safeguard is pointless, as it is nearly impossible to even scratch the megastructure. Only a direct Gravitational Beam Emitter blast is known to have been capable of digging a hole into a megastructure.
The City, and the Builders, were controlled by the Netsphere and the Authority but they have since lost the power to control the expansion of The City due to the chaotic and insecure manner of its growth. Without intervention by a user with Net Terminal Genes they cannot reestablish control over The City nor the Safeguards, whose original job was to eliminate any humans who try to access the Netsphere without Net Terminal Genes. The Safeguard now attempts to destroy all humans without the Net Terminal Gene as the degradation of The City has corrupted their true goals.
In regards to the scale of the structure, NOiSE, the prequel to Blame!, states in its final chapter that "At one point even the Moon, which used to be up in the sky above, was integrated into The City's structure". It has been suggested by Tsutomu Nihei himself in his artbook Blame! and So On that the scale of The City is beyond that of a Dyson sphere, reaching Jupiter's planetary orbit (32.675 AU, or roughly 4,901,250,000 km); this is also suggested in scenarios such as Blame! vol. 9, where Killy finds himself having to travel through a room roughly the size of Jupiter (roughly 143,000 km.).