Plot

Two friends with very different ideals start a beauty company together. One is more practical while the other wants to earn her fortune and live a lavish lifestyle.

Two friends with very different personalities run their own beauty company called Mia&Mel, Mel (Rose Byrne) (who is more business-savvy but lacks the confidence of her partner) & Mia's (Tiffany Haddish) (with a brash personality). The girls have been together since high school (best friends for 22 years) and even stay together in the same house. Mel is more practical, while Mia wants to earn her fortune quickly and live a lavish lifestyle.

Mel is angry with Mia forever delaying critical business operational activities and then hiding her faults or laziness under the garb of "product quality" and creating "scarcity". The business is under debt and doesn't generate enough cash. Mel is not able to confront Mia hard enough to change her ways and doesn't come completely clean about the dire state of the business.

Sydney (Jennifer Coolidge), Mel and Mia's co-worker and Barrett (Billy Porter) Mel and Mia's employee, generally make fun of the dysfunctional relationship between Mia and Mel.

Their friends (Jill (Natasha Rothwell), Kim (Jessica St. Clair) and Angela (Ari Graynor)) are worried that due to their involvement in the business the girls are missing out on having a family and kids, and that their time is running out. Mel and Mia move through one-night stands as their idea of a "relationship". In fact, they have created a product called "One Night Stand", their single use make-up kit.

Things take a turn for the worse when their company runs into debt, forcing them to turn to an unscrupulous benefactor who intends to steal the business out from under them. Claire Luna, the cosmetic mogul and owner of Oviedo, has been monitoring the online sales of "One Night Stand" ($21,000 in the last month) and sends her executive Josh Tinker (Karan Soni) to discuss a proposal to invest in Mia&Mel.

Mia refuses the offer as she says she values her independence. Mel talks to Mia about the financial situation of their store and says that they are in debt, and that they would have to close doors in 6 months if things do not change. Mel and Mia turn up to Ovieda offices for a meeting with Claire.

Claire Luna (Salma Hayek) obtains a controlling share of Mel & Mia's while bailing out the owners. Claire starts by offering to buy 49% of the company for settling $500K debt and investing a further $1.7 MM in the firm to help them expand. But really, she is after the new product innovations that Mel is an expert at.

Claire puts a condition that if one of the friends quit, Claire takes controlling stake (51%) in the firm. Mel and Mia agree, although Mia is not totally sold on it. Mel & Mia come up with a brilliant ad campaign for their new line, which Claire disparages. The ad campaign was about enduring friendships, and they record normal people on the streets, like themselves, who are best friends and have been together forever. The campaign is about boosting the best features of individuals (rather than hiding their flaws) and is called "Proud". Claire calls it too sentimental and cheesy. Claire also disparages the "One Night Stand" and says that the company needs a new idea. Mel pitches the 2 toned lipstick. Then she steals Mel's idea for 2 toned lipstick and then gets them to fire Barrett who hand produces Mel & Mia's custom cosmetics as Claire promises to mass produce their product for them.

The discussion with Barrett is really painful and drives a wedge between Mel and Mia. Mia accuses Mel of bending over backwards for Claire, while Mel believes that Mia is just jealous as Claire likes Mel more than she likes Mia.

After that Claire abruptly cuts off funding when Mel and Mia start missing deadlines. They have to go to her office and create a public scene, before Claire would grant them a meeting. Even then Claire tries to create fights between Mel and Mia, by always siding with Mel and showing Mia that even Mel doesn't agree with her ideas. Claire pitches Mel & Mia against Ron (Jimmy O. Yang) & Greg (Ryan Hansen), in a competition to see who does the best makeup. Mel & Mia lose, and Mel tries to please Claire, and Mia gets really angry saying that Mel it is giving up all her values to please Claire. They have a public spat and Mia quits the company.

Barret intervenes and tells Mia all the things that Mel has done for her in her life. Mia and Mel make up and realize that Claire has stolen their ideas and is presenting them at her launch party the same night.

Faced with the possible loss of their business, Mia and Mel approach Shay, Luna's former business partner, to start a new company, Proud Cosmetics, marketing their new 'Ride or Die' product, make-up intended to be used by best friends together to face their nights out. With this loophole, Mia and Mel can produce and market 'Ride or Die' under the 'Proud' banner while Luna takes ownership of Mia&Mel while still being required to pay Mia & Mel 49% of all subsequent earnings. Mia and Mel also bring along Sydney and Barrett to the new company.

Mel & Mia bring in all their friends, create a new product and crash Claire's launch party. They hijack the party and launch their new product. They also tell Claire that they launched a new company with Claire's ex-partner Shay (Lisa Kudrow) and their new product line is under the new brand. One year later Mel & Mia make it big as their new company goes international.