The NRLW premiership-winning Knight confirmed on Tuesday that Boyle and star fullback Tamika Upton would both miss the Jillaroos' World Cup campaign, with Upton succumbing to a calf injury.
It is Boyle's decision that could have greater ramifications though, after the best front-rower in the women's game informed Jillaroos coach Brad Donald on Tuesday of her decision not to tour England.
The Knights said Boyle made the call to prioritise her new business working with people living with a disability.
"Millie is all about team-first actions and putting her business and her participants' needs ahead of her playing ambitions is the very epitome of team first," Newcastle coach Ronald Griffiths said.
"Such is the nature of the women's game - these are not full-time athletes and as a result decisions are not as straightforward as they may seem.
"There are many factors to consider."
Boyle's call comes as negotiations continue between the NRL and Rugby League Players' Association on a new collective bargaining agreement, with both sides working on a deal for the women's game.
She has long been one of the loudest voices on the need to further professionalise the women's game, as one of the league's best and best-known athletes.
Women's players are still yet to learn what they will be paid for representing Australia in this year's World Cup, ahead of the first game on November 2.
That figure will likely be settled outside of CBA negotiations, and will be a significant increase on the $6000 payment for the 2017 tournament once finalised.
Upton's withdrawal came after she was troubled by a calf injury on the Knights' run to the NRLW premiership.
Long regarded as one of the world's best players, she was the Karyn Murphy Medallist as player of the grand final on Sunday.
She would have likely battled for a spot in the backline, with Sydney Roosters No.1 Sam Bremner named as one of Australia's co-captains.
Upton's withdrawal has opened the door for Emma Tonegato to join the touring party, after the St George-Illawarra fullback was controversially overlooked on Monday despite winning the Dally M in the first of two NRLW competitions played in 2022.
Tonegato's Dragons teammate Shaylee Bent has also been added to the squad.
"Tamika missed two games at the end of the longest year of her career to date and having managed the injury through the semi and grand final she needs to prioritise her recovery," Griffiths said.
"No doubt, sitting out a World Cup is one of the hardest decisions a player will make in their career.
"Both Millie and Tamika know that as a club we support them every step of the way."
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