Thirteen months and one pandemic later, “The Drew Barrymore Show” premieres Monday, with Barrymore taking center stage in her studio — and interacting with a virtual audience vis-à-vis COVID-19 protocols.

“There’s really an opportunity for innovation right now,” Barrymore, 45, told The Post. “The rule book is on fire.”

Barrymore said “The Drew Barrymore Show,” airing weekdays at 9 a.m. EST on CBS, was well-prepared for its launch amidst the current television climate of shooting remotely.

“When you think things may not happen, you take different risks when unprecedented times force you to think outside the box,” she said. “We call our audience our ‘virtual friends’ who I can talk to and build a community with. I really talk to our crew like they’re our [in-studio] audience. I want life and cacophony and noise and energy in and around the show. I tell them, ‘Please join in, be loud, say something if you want, laugh if you feel like it. This is not a hushed set.’

“It’s encouraged to be the exact opposite.”

The show will combine familiar elements such as (socially distanced) celebrity interviews — the premiere episode features her “Charlie’s Angels” co-stars Cameron Diaz and Lucy Liu. This week’s other guests include Reese Witherspoon, Charlize Theron, Jane Fonda, Adam Sandler and Billy Porter — with segments including “Drew’s News,” in which Barrymore takes viewers behind the headlines.

“I’m an obsessive information, news and pop-culture junkie,” she said. “When I aggregate so much information for myself, I find a lot of stories so fascinating beyond that front section of the newspaper or the top headline. I think [‘Drew’s News’] is a mixed bag, which is how I like digesting the information of the world — human interest, weird, fun facts. It feels like a newspaper where, to be a responsible citizen, you have to understand what’s happening in the front section but also in sports, metro, arts and sciences, business and even obituaries — which make me want to go and live a better life because someone else did and it’s very inspiring.”

The show’s online presence includes four digital docuseries: “Drew’s Movie Nite,” “The Art of the Interview,” “Drew’s Cookbook Club” and “The Making Of The Drew Barrymore Show,” which tracks the backstage run-up to Monday’s launch.

“It’s my way of avoiding the polish, like, ‘Hi, I’m here!,’ ” she says. “These are such extraordinary times and circumstances and there’s so much that takes to get to this moment. I thought it might be more informative to tell that journey rather than just see what’s out in front. I’m so much a part of what this show is, and will be, and as a consumer I want to know why these decisions were made, why this person was picked as a host, what’s the reasoning behind this?

“This has been such a wild endeavor that I decided to make a personal, behind-the-scenes documentary about what it’s all been like — so if you really want to know, this is a good way to find out,” she said. “People will see us come out of the gate with even more transparency and inclusion because this show has my name on it — but what’s most compelling for me is what I’m trying to make for other people.”

And, Barrymore said, she hopes to inject her well-known brand of humor and positivity into the show.

“I love optimism and happiness but I’m really desperate to show that happiness is a choice and the choice isn’t always easy,” she said. “It isn’t always available and it’s not just a silly, blind happiness, it’s the one we work for.

“You have to fight for it,” she said. “I can’t think of a better reward.”