2017–2021: Oil of Every Pearl's Un-Insides
In October 2017, Sophie released "It's Okay to Cry", her first new material in almost two years. The music video for the song was the first time Sophie's voice and image were used in a release. She subsequently opened up to the press about being transgender. Later in the month, Sophie also debuted in live performance, premiering newly recorded songs from Sophie's second album with vocal performances by Cecile Believe. The single "Ponyboy" was released with a self-directed music video on 7 December 2017. The third single from the album, "Faceshopping", was released on 16 February 2018 with a music video on 4 April 2018.
On 3 April 2018, Sophie announced via Instagram that the album was complete and that it would not be titled Whole New World as previously thought. On 1 May 2018, an interview with Crack Magazine revealed that the official album title is Oil of Every Pearl's Un-Insides. It was released on 15 June 2018 by Sophie's own label, MSMSMSM, along with Future Classic and Transgressive. The album prominently featured Sophie's own vocals. In early 2018, it was revealed in one of Sophie's tweets that she had contributed to and produced Lady Gaga's latest album. In a video posted on social media, when asked, Sophie said: "Yes. I mean whatever, you know. I work on a lot of different things. If it comes out, then it's cool. You can never tell. But she's a really cool person."
In July 2018, Sophie revealed work on four new projects, including a newly released debut album, which were all going to be released that year. Sophie said, "I have the next one finished... I'm going to release four albums this year". In an interview with Lenny Letter, Sophie said that she had done so much collaborating with other people that, "Basically, I've done a whole new album in the last two weeks." When asked to clarify whether this was a comment on EPs or albums, she stated that it would be "a mix". She had also been working with Kim Petras, Charli XCX, and Bibi Bourelly on new material within the year, as well as some rap collaborations in addition to the confirmed Lady Gaga collaboration.
At the 61st Annual Grammy Awards, Oil of Every Pearl's Un-Insides was nominated for Best Dance/Electronic Album, and Sophie made history as both one of the first openly transgender artists to be nominated in this category and one of the three first openly transgender women to be nominated for a Grammy. During a red carpet interview at the ceremony, she confirmed work on a remix album of Oil of Every Pearl's Un-Insides. In July 2019, Oil of Every Pearl's Un-Insides Non-Stop Remix Album was announced as part of an exclusive 3-CD set that included the original Oil of Every Pearl's Un-Insides album as well as a clutch bag featuring its artwork. The remix album was later released as two videos on YouTube on 29 July. Sophie featured on the September 2020 single "Metal" by Jimmy Edgar.
In January 2021, Numbers announced a new single release pairing a remix of "Bipp" by Autechre with the Product-era track "Unisil"; Sophie had previously stated that she wanted "NO remixes" of her music "unless it's Autechre" and called them "my heroes." The single was released two days before Sophie's death.