The character of Harriet Hayes is loosely modeled after Creator Aaron Sorkin's former girlfriend, Kristin Chenoweth.

Matthew Perry originally turned down the role of Matt Albie, but Aaron Sorkin did not want to have anyone else play the part, and apparently would not take "No" for an answer. Perry reconsidered, and decided to jump on board.

The last episode of the first season of the first three of Aaron Sorkin's television shows (The West Wing (1999), Sports Night (1998), Studio 60 on the Sunset Strip (2006), as well as the series finale of The Newsroom (2012), are titled "What Kind of Day Has It Been?"

The law firm of Gage Whitney Pace, employer of Mary Tate (Kari Matchett), was also the law firm at which Sam Seaborn (Rob Lowe's character on The West Wing (1999)) worked before joining the Bartlet administration.

There are numerous set-dressing items from The West Wing (1999) on display in various parts of the Studio 60 set, including the "NO TOURS BEYOND THIS POINT" sign, a "Bartlet For America" poster, and the seal of the President of the United States on the walls in the studios, and the Pirates of Penzance poster on display in Matt Albie's office.

Harriet's inability to tell a joke is based on Sarah Paulson's own inability t0o do so. Aaron Sorkin heard she had that problem, and thought it was hilarious, so he wrote it into the show.

Timothy Busfield (Cal Shanley) also directed five episodes of the series. Likewise, Bradley Whitford (Danny Tripp) directed the final episode of the series.

The episode title card and opening credits use the same font as The West Wing (1999), another show written by Aaron Sorkin.

The name 'Ricky Tahoe' (Evan Handler) is a reference to a conflict that Aaron Sorkin had with Rick Cleveland, one of the staff writers on The West Wing (1999). In this show, Head Writer Matt Albie dislikes Tahoe and his writing partner, Ron Oswalt, and often complains about his low opinion of their writing skills. In real life, Sorkin and Cleveland shared an Emmy for writing a "West Wing" episode, and after Cleveland publicly expressed disappointment that only Sorkin got to speak at the ceremony, Sorkin posted a claim on a message board that Cleveland's contribution to the episode was negligible. Sorkin claimed that he did almost all of the writing on "The West Wing", even when the writing credits claimed otherwise.

Immediately above the countdown board in Matt's office is a black-on-white strip bearing the legend "Time flies like an arrow, fruit flies like a banana. G. Marx"

The show's production logo features a picture of a shoe with the word "money" underneath. "Shoe Money Tonight" was the title of season one, episode ten of Sports Night (1998). It is a catchphrase that Dana Whitaker uses while playing poker with her boss, Isaac Jaffe.

The character "Andy Mackinaw" is loosely based on Studio 60 writer T. Rafael Cimino, the nephew of legendary film director Michael Cimino.

The title of the show was originally "Studio 7 on the Sunset Strip". The title was changed after it was discovered that there was a short-lived WB game show by the name of Studio 7 (2004).

Sarah Paulson and Nate Corddry are the only cast members to appear in every episode.

In Matt Albi's (Matthew Perry) office, there is a poster for the Pirates of Penzance. The musical and other works of Gilbert & Sullivan come up often in creator Aaron Sorkin's writings. In Sorkin's The West Wing (1999), there is an assistant White House Council, Ainsley Hayes (Emily Procter), who is obsessed with Gilbert and Sullivan. Her character is eventually replaced by a man named Joe Quincy, who is played by Matthew Perry.

When Matt Albie is trying to remember a writer in Studio 60 from the past, he comes up with the name "Tim Batale". It's later revealed that Matt is high, and is remembering himself in the past. The name "Tim Batale" is actually an anagram for "Matt Albie".