Using duplicates of himself in order to constantly learn new knowledge and abilities, Jamie Madrox formed a detective agency in District X with long-time friends Guido and Rahne. The agency was originally named XXX Investigators and their first case was investigating the murder of one of Jamie's duplicates. After the long and involved case, it was actually Guido who recommended changing the name of the agency to "X-Factor Investigations" as an homage to the superhero team to which they all once belonged. However, this new incarnation of X-Factor has no relation with the U.S. government, as the previous teams.
Jamie Madrox expanded the agency in the wake of House of M--adding Siryn and M--and began to investigate the mutant Decimation. Rictor, suffering from feelings of doubt and depression from no longer being a mutant, was pushed off the roof of a building by one of Jamie's dupes. After M saved Rictor from the fall, Jamie was able to convince him to join the agency as well.
Layla Miller added herself to the team as a way to prevent X-Factor Investigations from discovering the truth behind Decimation. The team soon learned the story despite her efforts, and subsequently took a public stand against the Superhero Registration Act.
In order to help the X-Men learn about the future following the birth of the first mutant baby since the Decimation, Madrox sent two duplicates into the future with Forge's help. Against the plan, Layla Miller joined one of the duplicates and ended up in the future timeline in which Bishop grew up. They were interned in a mutant camp, where Layla killed the duplicate in order to send his memories back to the original Madrox. She is still trapped in that timeline.
Wolfsbane left the team following the battle over the mutant baby and joined X-Force, though X-Factor Investigations doesn't yet know where she is.