Dealing with all the hoopla, the questions about the glory days and the dramatic exits, now will be left to general manager Jed Hoyer, who was Epstein's assistant GM in Boston.
"It'd be fun to watch those two teams play, and any chance to go home is always a lot of fun," Epstein said. "But I'll be there in spirit."
Perhaps Epstein will pull out the gorilla suit for old time's sake, a nod to the day he first quit as GM and left Fenway Park dressed in the furry outfit to avoid the media, only to return to the job a few months later.
Epstein had a legendary career in Boston, and is quoted in the book, "One Day at Fenway," as saying: "I thought it would take me years, if not decades, to earn a Led Zeppelin reputation for breaking things."
Now he says the story was a myth, and he only went along with it because it seemed like a cool thing to have done.
"Actually I slammed a door and threw my notebook across the room," he said. "And the Yankees scouts created this myth where I trashed the entire hotel room."
Myth-making aside, Epstein said he's disappointed to miss the series, which begins Monday, but noted he did return to Boston in late May for a dinner in honor of the 10th anniversary of the 2004 team that ended the franchise's 86-year championship drought. He saw a lot of former players he hadn't spoken to in years and former front-office colleagues.
But Epstein didn't attend the next day's on-field ceremonies at the park. Some former Red Sox players attributed that to his relationship with ownership, which soured during the fateful 2011 collapse.
"It's unfortunate," pitcher Tim Wakefield said. "But that's the way it is."
Epstein insisted the ceremony was for the players, and his presence wasn't really needed.
"I kind of don't spend any time thinking about those days," he said. "I've kind of totally moved on, and then it was kind of like a great high school reunion, bringing it all back. I enjoyed it."
Former Red Sox closer Keith Foulke said he didn't expect to see Epstein at all.
"It meant a lot to me that he came," Foulke said. "It was great to see him, great to talk to him. He had a lot to do with me coming (to the Red Sox) — well, everything — so I owe a lot to him."
Was it a shame Epstein wasn't being feted with the team during the ceremonies?
"Hey, he has a job, he's getting paychecks," Foulke replied. "I don't think he's too worried about it."
Epstein said he didn't need any recognition, and that he sees friends from the front office on occasion for "old stories over a couple of beers."
What type of reception would Epstein have received if he had walked onto the Fenway Park field this week for the first time since his departure for the Cubs job?
Most of those interviewed said Epstein would have been well received, perhaps with a nice ovation from Red Sox fans.
"But I'm not sure he would put himself in a position to get that," general manager Ben Cherington said. "I'm sure if he walks out onto the field he would get one, but I'm not sure he would want to walk out onto the field. We'll see."
Now that Epstein won't be making the trip, we won't see.
So what is his legacy in Boston?
Epstein was at the helm when the Red Sox ended the drought in '04, adding Foulke, Curt Schilling and others to a team that had lost a seven-game set to the Yankees in the 2003 American League Championship Series.
He traded local legend Nomar Garciaparra to the Cubs in a four-team deal that netted shortstop Orlando Cabrera and first baseman Doug Mientkiewicz, the biggest gamble of his career.
"We were a very talented group of guys brought together by a couple of GMs, Dan Duquette and Theo Epstein," former Red Sox outfielder Johnny Damon said. "Dan bringing a few of us here, and Theo pulling the trigger on one of the biggest trades in the history of baseball, trading away Nomar Garciaparra. … From top to bottom, from front office to the ownership to the fans, that's what made this special. Everyone should take credit (for) what the 2004 Red Sox team did."
The Red Sox won it again in 2007, but his relationship with the Red Sox owners and President Larry Lucchino went downhill, and they reportedly were happy to see him take the Cubs' offer after the great collapse of 2011.
Epstein said he spoke to Lucchino at the reunion dinner for the '04 team.
"Things are OK," he said, declining to elaborate.
"It's always special when our two historic and beloved franchises go at it in one of our iconic ballparks," Lucchino said. "And it is naturally a little spicier when you go up against former colleagues who have emigrated to the other side — like Theo, Jed and Jason (McLeod)."
In his third year running the Cubs, Epstein is excited about the progress he sees in the minors and said the pieces are in place for long-term success down the road.
But the major league team has been a flop each season, and Epstein has been Sphinx-like in Chicago after being a celebrity in Boston from his late 20s on. Fans rarely see him at the ballpark as he's usually spending his time in his office or in his Wrigley suite while avoiding being on field before games.
"I just enjoy the behind-the-scenes stuff more," he said. "It's part of the reason we have a bigger front office now. We can all focus on the parts of the job we're best at and we enjoy more. I've never really enjoyed the daily bantering with the media.
"I'd rather be out seeing players for the draft or talking to scouts. I try to be accountable, but not always present."
Cherington said Epstein, Hoyer and scouting director McLeod have "done exactly what they've set out to do" in Chicago, Cherington said, building a base and being patient.
"And they also knew that this is probably about the time that it starts to get challenging," he said. "Everyone wants to win, certainly the fans do and they do, and they know the best way to do that long term is to stay the course, stay with their plan. They have a lot of good young players coming, and they just have to stay the course.
"I'm sure they will. I'm sure they know Cubs fans are counting on it, and knowing Theo and Jed as well as I do, they take that to heart and they take responsibility for the team that's on the field and they know what they want to put out there also."
Still, some see Epstein leaving the organization when his five-year deal is up after 2016, pointing to his two high-profile exits in Boston and alleged frustration over the lack of resources he has been given at the major league level.
Epstein said he doesn't know why people think that.
"Maybe it's because I don't smile enough," he said with a grin.
He insists he will be here as long as the Cubs want him. So is Epstein now a full-fledged Chicagoan or just a refugee from his hometown?
"I consider myself both," he said. "I think I'll always be a Bostonian, but this definitely is my adopted hometown now. I love living here, my kid is in school and loving it. This is home now, and I'm lucky to have a home back East too."