The showdown between Letta and the head of his own party has been brewing ever since the now 39-year-old Renzi was elected in December and accused the government of dragging its feet over vital reforms.
The two failed to resolve their differences at a meeting on Wednesday and a defiant Letta ruled out resigning at a press conference later in the day in which he presented his reform programme for the year.
"The final clash is here. The fight between Enrico Letta and Matteo Renzi enters its last round today," said Claudio Tito, a columnist for La Repubblica.
"If the leadership of the Democratic Party confirms the criticism of the government expressed in these days, the prime minister will have to draw his conclusions."
Stefano Folli, an analyst for the Il Sole 24 Ore business daily, also said Letta could be on his way out.
Renzi "has to now strike the fratricidal blow in front of the television cameras today," he said.
The feud has exposed infighting within the centre-left party and one of the 140 members of the leadership committee, Pippo Civati, said he was concerned that Thursday's meeting could turn into an all-out duel.
"This is a time of great confusion," Civati said.
"The clash between Letta and Renzi is looking more and more like a struggle for power. The leadership meeting risks turning into a Western," he said.
Letta 'headed for resignation'
Most analysts predicted the imminent demise of Letta after less than a year in government and a "relay" with Renzi, who could take the prime minister's post and form a new government without a need for elections.
"Renzi is not giving up, Letta is headed for resignation," read a headline in La Repubblica.
Renzi has said he will address the party leadership meeting in Rome at 1400 GMT and "say what I have to say out in the open", while Letta has accused his rival of attempting a "palace manoeuvre" to unseat him.
"You don't resign over gossip," Letta said on Wednesday.
"It is absolutely not in my DNA to break with the continuity of service to this country," he said.
"Everyone has to express themselves clearly, especially someone who wants to come and take my place."
Letta said he would aim to fight unemployment and boost economic growth and was "proud" of his achievements in government despite operating in difficult conditions.
He said growth figures due out on Friday would confirm Italy's gradual recovery from a painful two-year recession that has pushed unemployment to record highs.
Renzi has accused Letta of being too slow in taking decisions and lacking the courage to confront key problems, such as the cost of Italy's bureaucracy.
Letta meanwhile has reportedly accused Renzi of "betrayal" since there had been a tacit deal that Letta would stay in office until at least the end of 2014.
Don't miss a story about Italy - Join us on Facebook and Twitter.