With elections due next year Khama is preparing to return home to bolster the opposition into a coalition to remove Masisi through the ballot box.
"I have to fix the mistake I made in appointing Masisi to be my successor," Khama told AFP in Johannesburg, adding he plans to "join with other parties to ensure that he (Masisi) and his party lose the elections."
South Africa-based Khama accuses Masisi, 60, of authoritarianism and has said he regrets having appointed him as his successor.
"It was a huge mistake, one that we are regretting as a country because he's totally undermined democracy, human rights, the rule of law, interfered with the judiciary."
Khama drew parallels between Masisi and ex-American president Donald Trump.
"Botswana has been a democracy, right from independence, we had a very good reputation for democracy, we were a shining light on the African continent, we were renowned worldwide for our adherence to democracy and then you get this one man who comes in one day and just overturns everything," said Khama.
"And this is the Botswana version of Donald Trump in Masisi."
The row between the pair started immediately after Khama resigned in 2018 at the end of his constitutional limit of two five-year terms when Masisi started reversing some key policies adopted during Khama's tenure.
Months later, and in the run up to the last elections, Khama dramatically quit the long-ruling Botswana Democratic Party, which had been co-founded by his father Seretse Khama, Botswana's first president.
The 70-year-old Khama governed one of Africa's most stable democracies and its top diamond producing nation for a decade until 2018, before handing the reigns to Masisi, then his deputy.
Khama landed in South Africa in November 2021 to meet Nigerian ex-leader and respected continental mediator Olusegun Obasanjo, who was trying to intervene to bridge the rift between both men.
He never returned home.
Khama, who is standing for presidency of his party next month, said he had intelligence information on plans to arrest and poison him if he returned home.
"They fear I have still got a lot of influence on the people of Botswana to be able to sway them, not that they need swaying, they pretty much made up their mind now that regime change should take place," he said.
On December 29 last year Botswana issued an arrest warrant for Khama, alleging unlawful possession of firearms.
In preparation for his return, he says he has undergone a full medical check and updated his will because he is almost certain that within days of arriving he will be locked up.
When he retired from power, the former senior military officer said he had intended to pursue conservation charity work, farming and that politics was not on his radar.
"When I left office I intended to completely leave politics but here I'm now more involved in politics than even when I was president because I'm determined to make sure this man (Masisi) goes," he said.