Herron’s maiden outing in 2014 ended in disaster when she dropped out of the race with only 6km to go.
She finished 10th in the 2013 Two Oceans before making her debut in the Comrades.
Last year the American distance ace withdrew a month before the race due to a partially torn hamstring injury.
Running in the colours of Nedbank Running Club, the 35-year-old will be returning with high hopes of breaking South Africa’s iron grip over the last two years.
“My first running book in Junior High School was Lore of Running (by Tim Noakes), so I’ve been reading about the Comrades since 1995,” Herron said.
“It’s the pinnacle of ultras. I’ve already got two world titles and to win here would be huge to my career.”
In 2015 Caroline Wostmann became the first South African woman in 14 years to win the Comrades Marathon with former training partner Charne Bosman upsetting her for the title in 2016.
Herron believes her experience from 2014 will hold her in good stead as she looks to add the prestigious Comrades title to her long list of accolades.
The year following her Comrades disappointment saw a major breakthrough for her - she won the International Association of Ultrarunners World 100K Championship title in Winschoten, The Netherlands, in the fourth fastest time by woman, clocking 7:08:35.
“I got to experience it a bit in 2014, although I was ill at the time and passed out at 83km,” Herron said.
“I loved the energy, people, history, and have wanted to come back and see my talent through to the finish.
“You can really sense and appreciate what this race means to South Africans. I’m grateful for the support from the Nedbank Running Club and will give it my all.”
Herron will go into the Comrades Marathon buoyed by her early season form, winning New Zealand’s Tarawera Ultramarathon (102km) trail race in February.
She has set her sights on becoming only the second woman, behind compatriot Ann Trason to win both the Comrades Marathon and the Western States 100 (160km).
Trason achieved the “double”, winning the Western States just 12 days after winning the Comrades Marathon.
Herron will have to contend with Bosman and Wostmann’s experience in racing the Comrades Marathon, however, with the duo set to put up the biggest resistance.
Wostmann suffered a setback in her Comrades preparation after she dropped out of the Two Oceans in Cape Town last month due to an injury but was on the road to recovery.
The ultramarathon is on June 4.