Marlo Thomas, the actress, activist, and author of It Ain't Over...Till It's Over, has worn many hats over the course of her more than 50-year career. Taking on the role of a business executive, however, came as a surprise.

"My father could never have talked me, my sister, or my brother into doing this," said Thomas, referring to the late Danny Thomas. He founded St. Jude Children's Research Hospital, where Marlo Thomas now serves as the national outreach director. "It's not something that you can just do on paper. It's something that hits the heart," she continues. "I wasn't intending on running the whole program."

Yet today, more than a decade later, Thomas continues to oversee the hospital's outreach. In 2004, with the help of her two siblings, she created the national "Thanks and Giving"campaign to raise funds for research into childhood cancer and other life-threatening diseases.

Each year during the months of November and December, consumers are encouraged to donate through participating retailers (Kmart, Best Buy, and Domino's are just a few of the more than 70 brands partnering in the campaign). Celebrity partnerships also help boost customer awareness for St. Jude. Most recently, Jimmy Kimmel, along with returning partners Jennifer Aniston, Sofia Vergara, and Michael Strahan, have taken part in a series of St. Jude television commercials.

To date, the "Thanks and Giving" campaign has raised nearly $600 million ($588 million.) In 2014 alone, it raised $100 million. Remarkably, even during the peak of the economic recession, Thomas reports that funding was up by 30 percent. This season, she aims to hit $110 million -- adding that, so far, St. Jude is on track to raise at least $100 million.

"The basis of the success [of St. Jude] is that people know it's genuine," she said, referring to the fact that families who come to the hospital never have to pay for things like care, travel, and food and board. All said, it takes roughly $2 million each day to live up to that promise -- made possible, in large part, because of the money raised annually through "Thanks and Giving."

It is a business, after all.

In many ways, running a charity campaign is very similar to growing a startup, and Thomas isn't shy to say that she's faced many challenges.

"National campaigns are expensive," she said, adding that this campaign needed to be free of charge for the hospital itself. The solution? Get the retailers to do the heavy lifting.

In addition to having donation options at check-out stands and online, some brand partners have created related merchandise, such as plush toy animals from Kay Jewelers, where proceeds go directly to the hospital.

"We believe that doing good is good business," said Jamie Stein, a Kmart spokeswoman. The chain of department stores is St. Jude's No. 1 highest grossing brand partner. Since 2006, it has brought in over $76 million in donations. 

Thomas says that winning over brand partners wasn't hard. The real challenge is coordinating operations and maximizing efficiency across retail locations. In the beginning, she recalls naively expecting to be able to raise $100 million in the first year. They ended up earning $8 million.

Having been inspired by the national Take Our Daughters to Work initiative--which aims to raise awareness for women in business --Thomas initially conceived of the campaign as lasting for just one day, rather than for two months. "It turned out to be way bigger than what I expected it," she said.

Thomas notes that the biggest challenge with "Thanks and Giving" has always been operational. "We run it like a business, because it is a business," she says. 

To that end, Thomas gets together with the CEOs and CMOs of the corporate partners once a year, to share "best practices," and to discuss the bigger challenges. It's a big agenda, and the meetings tend to run for more than five hours each time.

Finding what works. 

One tactic that helped to increase donations was introducing PIN pads to the check out process. Best Buy, which is currently in its third year with the campaign, raised $1.9 million in 2012. By incorporating the PIN pads, donations topped $9 million the following year. "That certainly helps the traffic move quicker," Thomas notes, though convincing the retailers to implement the technology -- which was an additional expense for them -- wasn't easy at first.

The founder's personal touch shouldn't be underestimated as your organization grows. "We figured out that the stores liked  hearing from me," Thomas says. In addition to sending out a message to retailers at the beginning of the campaign, she now also sends a message in the middle of the season, to get a sense of how well they're doing.

Much as Thomas was influenced to join the board of St. Jude by interacting directly with children, she's confident that exposing the public to true stories through television ads will also reap more donations.  "You're seeing real families. The children tell the story of St. Jude better than I could," she says.