Samantha, who has been vocal about Meghan's union to Prince Harry since their first public debut as a couple in 2017, penned an op-ed piece in The Sun on Monday, slamming Meghan for using her romance to Harry to achieve fame and splitting up the royal family in the process.
Samantha first defends the queen in her letter, crediting Her Majesty for wanting to repair the damage in her latest statement supporting Meghan and Harry's decision to "step back" as senior royals.
"Her Majesty's words show great diplomacy but Meghan's behavior has so far not been diplomatic," her sister wrote. "A diplomat wouldn't fall out with her own family."
Meghan's sister also accused the former "Suits" actress of failing to defend their father, Thomas Markle, who she said is currently "frail" due to a heart condition.
"[Thomas Markle] doesn't have a PR team to spin him a good story," Samantha claimed. "The Queen, at 93, shouldn't have had to face the stress of seeing her family torn apart. Meghan hasn't stepped forward to minimize the damage. She knows how Harry leaving has affected them, but she hasn't spoken up in their defense."
Samantha blasted Meghan for becoming a "totally different person" than the sister she once knew for "choosing wealth and fortune over family."
"My fear is Meghan’s decision isn’t about moving to Canada for a quiet life as a young mother. Nothing about their actions so far suggest they truly desire a private life out the limelight. They have paraded themselves on the red carpet, tried to make deals with Disney, and become pals with the Clooneys and other A-list stars.
"Smooching up to Vogue magazine, to fashion and to the film industry is not consistent with taking a step back. Their objective is fame and fortune — to be Hollywood," Samantha added.
The estranged sister pointed out all the ways the royals tried to embrace Meghan, who is half African-American.
"Her marriage to Prince Harry was so symbolic of ethnic unity. The preacher and choir were all of African heritage. It was a lovely joining together," Samantha said, referencing Meghan and Harry's 2018 nuptials.
She continued: "The royals embraced that. They welcomed Meghan into their lives, into the culture, and allowed her to promote people of all races. I have never heard anything racist coming out of the Windsors about my sister."
On Monday, Prince Harry traveled to Canada to reunite with Meghan and their eight-month-old son.
Samantha said she fears Meghan and Harry will not have a promising future no matter where they are.
"I am worried that Meghan and Harry will never find true happiness," Samantha wrote. "They could not find contentment with the Royal Family, will they be able to find it away from them?"
On Jan. 8, Harry and Meghan announced they would take a "step back" as senior members of the royal family and instead work independently, splitting their time between the United Kingdom and North America, specifically Canada.
The queen accepted the couple's desire on Saturday, with Buckingham Palace releasing a statement that the duo will no longer be referred to as his or her "royal highness". They will retain their titles of Duke and Duchess of Sussex, and Harry will still be known as Prince Harry. Meghan's husband also still remains sixth in line to the throne.
Fox News' Stephanie Nolasco contributed to this report.