It will be the fourth time the firebrand anti-American populist, re-elected only last October, has undergone surgery since being diagnosed last year.
But this time there was a more ominous tone as Chavez, whose country sits atop the world's largest proven oil reserves, spoke for the first time of the idea of succession, naming foreign minister and vice president Nicolas Maduro as his favoured heir apparent.
Chavez disclosed his upcoming surgery Saturday night, shortly after returning from 10 days of treatment in Cuba.
The announcement shocked people who have come to know him as an indefatigable and garrulous man who was a fixture of their everyday life.
"He will live! He will live! The commander will live," an assembled crowd chanted Sunday in Bolivar Square in downtown Caracas.
Vladimir Hernandez, 52, said it hurt him to hear Chavez was due for more surgery. "Now I am here to ask God to help us in these hard times," he said after joining the throng.
Chavez, 58, had said he was cancer-free after being diagnosed last year and treated. But he dramatically announced Saturday that malignant cells had returned and that he needs more surgery.
Treatment is "absolutely necessary," the leftist leader said in a bombshell statement on state television in which he admitted he may have to give up the presidency and that Maduro was his chosen successor -- a move analysts saw as the first step of a political transition.
The designation of an heir apparent in the event that "something happened" to him underlined the seriousness of Chavez's condition, which he said was causing his strong pain and required him to take tranquilizers.
In power since 1999, Chavez has made repeated trips to communist Cuba for cancer treatment since his original diagnosis.
Over the past year and a half, Chavez has missed practically every regional meeting he was to have attended, including the Summit of the Americas in Colombia, the Mercosur summit in Brazil and last month's Ibero-American summit.
He returned Friday after his latest stay in Cuba, during which his medical team stressed a sense of urgency about the looming operation, his fourth since mid-2011.
"The doctor recommended that I undergo surgery yesterday (Friday) at the latest, or this weekend," he noted. "But I did not agree and came back home."
In what appeared like a presentation of his final will, the once-omnipresent leader, who had not been seen in public for three weeks, urged Venezuelans to vote for Maduro in the next presidential poll should he become incapacitated.
"Choose Maduro as president of the republic," Chavez said. "I am asking you this from all my heart."
Maduro, who has been serving as Venezuela's foreign minister for the past six years, was appointed vice president in the wake of October's presidential poll. He has since held both portfolios.
The 49-year-old former bus driver who began his political career in the labor movement belongs to the more moderate wing of the Chavez entourage.
Paving the way for his departure, the National Assembly on Sunday granted Chavez permission to travel to Cuba and, in another possible indication of the seriousness of the matter, leave the country for an indefinite amount of time.
Under the Venezuelan constitution, if a new president is incapacitated before inauguration -- scheduled for January 10 -- fresh elections must be called in 30 days. The parliamentary speaker must then take charge until a new president is elected.
If incapacitation or death occurs after the inauguration but in the first four years of a term, the vice president takes over and governs until an early election determines a new leader.
Exactly what type of cancer Chavez has remains a mystery since the longtime leader has handled his illness as a state secret.
Prior to Saturday's announcement, he had repeatedly claimed to have beaten the unspecified cancer and shrugged off his illness to see off a unified opposition and win power again.
Chavez appeared weak and subdued during the presidential campaign, but still managed to win another term that extends to 2019.