Higuain, who recently revealed he could play in Major League Soccer before he retires, has had a weird couple of years, spending the 2018/19 season on loan at two separate clubs - Milan and Chelsea - before returning to Turin to play for old Napoli manager Maurizio Sarri.
Khedira was a big hit during his first three seasons with Juve following his move from Real Madrid in 2015, but recent years have seen the World Cup winner hit by injuries. The 33-year-old has made just 22 Serie A appearances in the last two campaigns.
Now, Fabrizio Romano has revealed neither player will be part of Andrea Pirlo's plans for the Serie A side. Talks are ongoing over the payments for the remainder of their contracts, with both still having a year left to run.
Higuain started 20 league games under Sarri last season, returning eight goals and four assists, while Khedira has fallen firmly behind the likes of Rodrigo Bentancur, Adrien Rabiot and even Aaron Ramsey, who himself had an injury-hit campaign.
Blaise Matuidi's departure to Inter Miami was recently confirmed, while Arthur has been drafted in from Barcelona in exchange for ageing midfielder Miralem Pjanic.
Higuain's effectiveness declined as Juve elected to play to the strengths of Cristiano Ronaldo up front - often to their own detriment, even though the Portugal legend ended the season with 31 league goals.
Juve are going for a tenth Serie A title in a row next season, though it might be a trickier proposition than it has been in recent years. Lazio ran them close but failed to capitalise on La Vecchia Signora's slip-ups and Inter are expected to make a tougher challenge, while Atalanta may also have designs on the title, having finished third.