In the upcoming comedy, Second Act, Lopez plays Maya Vargas, a street-smart New Yorker who gets passed over for a promotion at big-box store The Value Shop after 15 years of service in favor of a candidate with a college degree.
"She takes the opportunity to prove that street smarts can sometimes be more valuable than book smarts," Lopez told PEOPLE.
Ventimiglia plays Maya's boyfriend, Trey — and from the sound of things, Lopez wouldn't have it any other way. "I'm a huge fan of This Is Us," Lopez admitted. "He brings such depth to everything he does, and he was our first and only choice for Trey. I loved every second working with him. Besides being an incredible actor, he's a great person."
Lopez's real-life best friend Leah Remini plays Joan, who helps Maya try to succeed in the corporate world. Lopez said their real-life friendship shines through on-screen thanks to their natural chemistry.
"We have an ease and natural chemistry that I think is reflected on screen," Lopez said of Remini. "During filming, we'd try different things in different takes to make each other laugh, or push each other further. I'd go, 'Do that thing you do,' and then we'd just start riffing. We'd be totally off script, and having a ball."
Lopez says fans will leave the theater after seeing Second Act feeling empowered and ready to take on their dreams. "It is a comedy for anyone who dreams big and asks, 'Why not me?'" she said.
Also starring Vanessa Hudgens and Treat Williams, Second Act hits theaters on Nov. 21. Meanwhile, Ventimiglia will star in the third season of This Is Us, set to premiere on NBC on Tuesday, Sept. 25.
Ventimiglia's co-stars Mandy Moore and Chrissy Metz have teased the premiere episode of season 3 as particularly emotional, with both actresses revealing that they shed tears while separately reading the script.
"Reading the first episode of [This Is Us] season 3, followed by [Queer Eye] is NOT for the faint of heart," Moore captioned a selfie on her Instagram Story in June.
Metz said the script made her cry so much while on a plane that a flight attendant asked if she was OK.
"Just read our season 3 premiere episode on the flight home... The flight attendant asked if I was okay... still not sure," Metz wrote, also in June.