Middle-aged best friends Barb and Star leave their home of Soft Rock, Nebraska for the first time to go on vacation to Vista Del Mar, Florida.

Upon arrival, they find accommodations at the luxurious Vista Del Mar Hotel and resolve to try many excursions, particularly an inflatable banana inner tube ride.

Sharon lived there as a child, and her pale white skin and sensitivity to the sun made her an outcast and a target of bullying.

She sends her henchman, Edgar, to Vista Del Mar to plant a homing beacon that will attract the mosquitos once they are unleashed.

Star also meets with Edgar, but despite feeling conflicted about Barb, continues to have a sexual relationship with him in secret that develops into romance.

Edgar fights Darlie, while Star and Barb escape with the beacon, taking a jet ski out to sea to save the town.

Star recognizes that Sharon's hostility is born from her bullied childhood, and having never experienced true friendship (with the exception of a girl who befriended her only to be immediately eaten by an alligator).

The film was officially announced in April 2019, having been in production for a number of years, with Annie Mumolo and Kristen Wiig, the co-writers of the screenplay, set to play the titular characters, and Josh Greenbaum directing.

Wiig and Mumolo also produced, alongside Jessica Elbaum, Will Ferrell, and Adam McKay, under the Gloria Sanchez Productions banner, with Lionsgate distributing.

[14] In its second weekend, the film finished fourth on Spectrum, fifth on FandangoNow, sixth on Apple TV, and seventh on Google Play.

The website's critics consensus reads, "Bright, colorful, and unabashedly silly, Barb & Star Go to Vista Del Mar reaffirms that Annie Mumolo and Kristen Wiig are still as fun—and funny—as ever.

"[16] According to Metacritic, which sampled 30 critics and calculated a weighted average score of 64 out of 100, the film received "generally favorable reviews".