Teodoro Obiang Mangue
, who is also the vice president of the Gulf of Guinea nation, was handed a three-year suspended sentence and a 30 million euro ($33 million) fine at the end of his trial in absentia in 2020.
Luxury assets seized in France during the investigation were ordered to be confiscated.
Obiang has always denied any wrongdoing and argued that French courts had no right to rule on his assets, but the Cour de Cassation rejected his appeal.
"With this decision ... France is no longer a haven for money embezzled by senior foreign leaders and their entourage: the assets acquired in France with dirty money will be confiscated and their owners prosecuted and condemned," Patrick Lefas, of Transparency International France, said in a statement.
An Equatorial Guinea government spokesperson did not immediately respond to a request for comment.
The residence at the center of the dispute is a luxury residence on Avenue Foch in Paris
-- a grand, sweeping road near the Arc de Triomphe. It has 101 rooms, a gym, a hair-dressing studio and a disco with a cinema screen.
Now that there can be no more appeals in this case, the assets are set to be put on sale under a new French law which stipulates that the money, instead of going to the French state's coffers, should go back to Equatorial Guinea.
That would be a first. It could be done via local or international NGOs or France's development aid fund.
Obiang's father, President Teodoro Obiang Nguema Mbasogo
, has ruled Equatorial Guinea since taking power in a coup in 1979, 11 years after independence from Spain.
Exploitation of the country's oil reserves over the past few decades has greatly increased the size of its economy. More than 76% of the population, however, continue to live in poverty, according to World Bank figures.
Other cases of alleged misappropriation of funds by foreign officials are lined up in France and could potentially also end up with decisions to return money to the affected populations.
A French court has found the exiled uncle of Syrian President Bashar al-Assad, Rifaat al-Assad, guilty of acquiring millions of euros worth of French property using funds diverted from the Syrian state. An appeal is still pending in that case. He has denied any wrongdoing.