The series was developed by NBC News Studios, a company launched after NBC shut down its unscripted unit Peacock Productions in early 2020, in partnership with Blumhouse Television to adapt true crime stories from Dateline NBC into scripted programming.

The show is based on Dateline NBC's coverage of the case and is named after a Dateline podcast from 2019 also called The Thing About Pam.

Renée Zellweger joined the project in February 2021 to portray Pam Hupp, marking her network television debut, and also became an executive producer through her production company Big Picture Co.

Writer and original showrunner Jessika Borsiczky exited the series in August 2021 due to creative differences, remaining only as an executive producer, and was replaced by Jenny Klein as showrunner.

Filming, which took place in New Orleans and Hammond, Louisiana, was postponed due to Hurricane Ida, pushing the start date to October 1, 2021.

Makeup artist Arjen Tuiten spent up to eighty minutes applying facial prosthetics on Zellweger, with the full transformation taking two to four hours; Zellweger noted she is allergic to the adhesives used, requiring Benadryl during the process.

When asked why an actress more physically similar to Hupp wasn't cast instead of using extensive prosthetics on Zellweger, executive producer Chris McCumber said that when a two-time Oscar winner asks to play and produce the role, the answer is simply yes.

Composers Giona Ostinelli and Sonya Belousova created a distinctive score using an English horn, a prepared piano with coins between the strings, a harmonica, 'ka-ching' sounds, a custom Italian instrument combining a waterphone and daxophone, and a slurping sound effect they devised before filming began.