Hospital Playlist is the second installment of the Wise Life series, following Prison Playbook (2017–18), and reunites screenwriter Lee Woo-jung with director Shin Won-ho, who previously collaborated on the Reply anthology series.

It took four years for the script to be completed before production began.

To comply with the 52-hour work week system and avoid overnight filming for the sake of the cast and crew's health, the production team chose to air one episode per week over twelve weeks instead of the usual two episodes per week over eight weeks.

Some hospital scenes were filmed at Hallym University Dongtan Sacred Heart Hospital and Ewha Womans University Medical Center, but later season one scenes set at these locations had to be shot on a set due to the COVID-19 pandemic.

Filming for season two, originally scheduled to begin in early December 2020, was postponed to late January 2021 due to the COVID-19 pandemic and wrapped on September 6, 2021.

Director Shin Won-ho initially envisioned Hospital Playlist as a three-season series to be released over three years, but expressed uncertainty about a third season after season two due to exhaustion and other issues, even though the cast and crew said they would be willing to return.

The season one soundtrack consists of covers of popular Korean songs from the 1990s and 2000s, and was praised for how these remakes appealed to listeners of all ages.

The season two premiere recorded a 10.007% nationwide viewership rating, the highest premiere rating in tvN's history, and the finale reached 14.080%, the season's highest rating.

The drama is credited with boosting public interest in organ donation in South Korea; after registrations dropped in 2020 due to COVID-19, they rose by 35.7% by 2022, an increase attributed partly to the show's warm depiction of various donation stories.