It was announced in April 2021 that Robyn Lively joined the cast as Miss Bellum and Tom Kenny, who narrated the original animated series, will return to narrate the live action pilot. This version of Miss Bellum is described as a "warm and witty career woman who has a complicated romantic history with Professor Utonium (played by Donald Faison). Always a friend to the Powerpuff Girls, she has remained close to them since childhood."
After three years in development, the CW network announced on May 22, 2023 that the planned series had been cancelled following the network's acquisition by Nexstar Media Group.
It was announced May 24, 2021 that the CW wasn't impressed with the pilot, so the network will film a new one off-cycle. The four leads -- Chloe Bennet, Dove Cameron, Yana Perrault and Donald Faison -- as well as other cast and the writers-producers all remain on board the project. The CW chairman and CEO Mark Pedowitz explained that "This was just a miss. We believe in the cast completely. We believe in Diablo and Heather [Regnier], who are writing, and we believe in the auspices of Greg Berlanti and Warner Studios. In this case, the pilot didn't work. Tonally, it might have felt a little too campy, and didn't feel as rooted in reality as it might have felt. We see there's enough elements in there, so we wanted to give it another shot. And so in this case, we said, 'Let's take a step back and go back to the drawing board.' Because this is a powerful property. It has engaged a lot of interest, and we want to get it right before we put it out."
The live-action series adaptation was first announced by Warner Brothers studios and the CW network as being in development back in August 2020.