The film covers Susann's entire life, focusing on her early struggles as an aspiring actress relentlessly hungry for fame, her relationship with press agent husband Irving Mansfield (Nathan Lane), with whom she had an institutionalized autistic son, her success as the author of Valley of the Dolls, and her battle with and subsequent death from breast cancer.

In addition to Midler and Lane, the film stars Stockard Channing as Susann's "gal pal" Florence Maybelle, David Hyde Pierce as book editor Michael Hastings, and John Cleese as publisher Henry Marcus.

"[5] Elvis Mitchell of The New York Times praised Midler, Lane, and Cleese, but opined that screenwriter "Rudnick and the director Andrew Bergman (The In-Laws, 'Honeymoon in Vegas') have so defanged 'Isn't She Great' that it's like watching a sketch from the old 'Carol Burnett Show' that has mildewed.

The showbiz feel is the film's main aim, inferred by the casting of klieg-light legends Midler and Lane, and by delineating Susann as a wannabe who succeeded in gaining the world fame of an entertainer.

"[9] Polygram Records released a soundtrack album containing "On My Way" and "The Book Tour (On My Way – Reprised)" by Dionne Warwick, "Open Your Heart" by Vanessa Williams and 14 instrumentals by Burt Bacharach.