Storylines abound at Mission Hills in Rancho Mirage, including the continuing rise of the Korean juggernaut and a possible overdue major challenge by super-talented Jessica Korda.
Straight-hitting Feng assumed the world number one ranking in November, becoming the first player from China to occupy top spot.
Her record at Mission Hills is spotty -- only two top-10s in eight starts -- but her chances are looking up this year, with a healthy growth of rough likely to put a premium on accuracy.
"I don't even know why I've never really played super well here," Feng told reporters on the eve of the tournament on Wednesday.
"Hopefully this year I can make my record become a little bit better.
"I think I'm still working my way out there to try to get my A-game back. I think my putting is improving a little bit. So hopefully this week everything will be there."
Former child prodigy Wie, meanwhile, is brimming with confidence after her unlikely victory in Singapore on March 4, when she holed her winning putt from off the green at the final hole.
Good health has also helped her confidence, after a few years of dealing with multiple injuries, something she has discussed with Tiger Woods.
"Every time we see each other we list off all the things. How's your ankle, how's your back, how's your everything? And then it's a 20-minute conversation, and then we can move on from there," Wie said.
"I think I have osteoarthritis in a couple spots in my wrist. So my doctors and I, we've been taking these collagen injections which is what helps to build the cartilage.
"It just sucks that it's on both wrists, so I have to go in and out of the doctor's office quite often.
"When your back is hurting or neck is hurting, you can't really do much. It definitely helps to not have your hands hurt when you putt."
Another to watch this week is defending champion Ryu So-yeon, who heads a formidable South Korean challenge that includes five of the world's 10 top-ranked players.
Korda is also a realistic contender after her recent victory in Thailand, and she is on a mission to correct a spotty major record.
"This year I've honestly been feeding off of what I was doing last year," said Korda, who had jaw surgery in December to alleviate excruciating headaches.
The five-times LPGA winner and her younger sister Nelly are two of the brightest talents on tour, daughters of the 1998 Australian Open tennis champion Petr.
The ANA Inspiration kicks off a major season that visits some storied courses.
The U.S. Women's Open will be played at Shoal Creek in Birmingham, Alabama, site of the 1990 PGA Championship on the men's tour, while Royal Lytham hosts the Women's British Open. (Reporting by Andrew Both in Cary, North Carolina Editing by Toby Davis)