In 2004 he wrote the "4th Parallel" storyline for the Justice League which introduced the Red King; this story was published in 2007 in JLA Classified #32–36.

While She-Hulk was on hiatus in 2005, Slott penned the Spider-Man/Human Torch miniseries, which chronicled the friendship of the two characters over the years, with each issue paying tribute to a different era of Marvel Comics.

Slott gave the team the Great Lakes Avengers their first ever solo miniseries in GLA: Misassembled, which featured a character being killed in each issue.

He has since returned to the GLA twice, first with the 2005 GLX-Mas Special, following a name change to the Great Lakes X-Men, and then again in the 2007 Deadpool/GLI Summer Fun Spectacular with co-writer Fabian Nicieza, to coincide with Marvel's Civil War: The Initiative branding.

The eight issues have been released in a trade paperback entitled Idol of Millions, which sees the Thing and other heroes fighting deadly roller-coasters and other machines in Arcade's Murderworld.

[22] He wrote his last major storyline, titled "Go Down Swinging", from issue #797–800, which detailed Spider-Man fighting a Carnage-bonded Green Goblin.

After finishing his run on The Amazing Spider-Man, Slott began writing Tony Stark: Iron Man and Fantastic Four.

[24] In May 2021, Slott publicly apologized for the sexualization with which he wrote the relationship between Peter Parker and Cindy Moon/Silk, an Asian character he co-created.

Slott would be joined by artist Mark Bagley on the book, which would tie into Zeb Wells and John Romita Jr.'s The Amazing Spider-Man series.