As part of the deal Archer struck to secure the co-operation of the Xindi Aquatics in destroying the weapon, he promised that Enterprise would destroy the sphere network once and for all. Fortunately Trip and T'Pol had by this time come up with a feasible plan to do just that, and whilst Archer pursued the weapon T'Pol took Enterprise to sphere 41 to implement the plan. 
The plan involved using the deflector dish to transmit a specific energy pattern to the sphere, causing it to implode and in the process transmit the energy on to the next sphere in the network, and so on. Unfortunately on arrival the crew discovered that the sphere was surrounded by a super-anomaly. Phlox was able to devise a way to protect the crew against the effects for a brief time, and the ship proceeded into the anomaly. 
The Sphere builders, determined to prevent the defeat of their plan to invade the Milky Way galaxy, boarded Enterprise and attempted to damage the power systems. Thanks again to Phlox the MACO team on board was able to modify their weapons to a frequency which the Builders were vulnerable to and beat them back. Enterprise was successful in destroying sphere 41 with just seconds to spare, and as predicted the entire network was brought down. The many anomalies of the Delphic Expanse almost immediately began to clear; even the thermobric clouds surrounding the area dissipated rapidly, returning the whole region to normal space again.