The series is loosely based on the real-life podcast 'Dying for Sex', co-created by Molly Kochan and her friend Nikki Boyer, which recounted Kochan's journey of sexual exploration after being diagnosed with terminal stage IV breast cancer. Kochan died on March 8, 2019, at age 45, and her podcast and memoir 'Screw Cancer: Becoming Whole' were released the following year.

Creators Liz Meriwether and Kim Rosenstock had started as playwrights before working together on Meriwether's 'New Girl'. Meriwether received the podcast in March 2020 while working on 'The Dropout', and the series was commissioned that same month.

Meriwether and Rosenstock began writing the show months into the COVID-19 pandemic and had no direct narrative or tonal comparison to draw from, though they were inspired by 'I May Destroy You' and the sex scenes in 'Normal People'. They also consulted sex educator Emily Nagoski for Molly's orgasm scene.

Michelle Williams first spoke with the creators via Zoom in 2022 after being reduced to tears by the podcast, but initially declined the project because it was set in Los Angeles. She eventually signed on after her daughter became obsessed with 'New Girl' and after a chance meeting with Meriwether at the 2023 Critics Choice Awards, where Meriwether mentioned she was moving to New York.

The role marked Michelle Williams's first TV role since 2019's 'Fosse/Verdon' (for which she won an Emmy) and included her first-ever masturbation scene on screen.

Jenny Slate joined the cast after a chemistry read in late 2023; at the time she had paused looking for other jobs while waiting for a project with depth and breadth.

Rob Delaney, who plays Neighbor Guy, had previously been public about his experiences with grief after losing his toddler-aged son to a brain tumor.

Filming began in March 2024 in New York City; one particular scene, in which Michelle Williams's character kicks Rob Delaney's character in the penis, was filmed repeatedly for more than half a day.

The show contains extensive male nudity, to the point that FX asked the creators to tone it down slightly, though Michelle Williams never appears nude herself.

The writers took several creative liberties from real events: Kochan had already experienced her first orgasm before her cancer treatment declined her sex life with her husband, the femur-breaking incident and the pet hospital visit were fictional additions, many of Kochan's real-life kinkier partners were merged into the single 'Neighbor Guy' character, and the setting was changed from Los Angeles to Brooklyn.