The high-stakes vote came as new developments Friday put added pressure on the government to help the country navigate its economic crisis.
On Friday morning the Labor Department released numbers revealing that employers cut 159,000 jobs in September, marking the ninth month in a row that employment numbers have declined.
And Wachovia Corp. said it would be bought by Wells Fargo for $15.1 billion.
The House's rejection of an earlier version of the package triggered a 777-point plunge in the stock market Monday.
The House approved a bill packed with $100 billion worth of extra incentives than Monday's proposal had.
The additions were intended to appeal to the 133 disapproving House Republicans that helped vote down the measure earlier this week.
Some of the goodies intended to attract the votes of individual members of Congress include $192 million to divert taxes paid by the rum producers from the federal government to the governments of Puerto Rico and Virgin Islands, $128 million for car racing tracks, $33 million for corporations operating in American Samoa, and $10 million for small film and television productions.
Other Senate modifications with much broader appeal includes a provision that gives the Treasury Department the authority to buy troubled mortgage securities.
The bill also now includes an extension of numerous tax breaks for research and development and renewable energy companies, as well as personal tax breaks for college tuition and disaster victims.
It proposes adjusting the Alternative Minimum Tax, so it doesn't hit more than 20 million middle class Americans in 2009.
Another key modification is a one-year increase in the limits of personal bank savings the government insures up to $250,000.
Still, despite promising support building on the Republican side, some worried that fiscally conservative House Democrats would not support the bill's tax cuts that are not paid for in the budget.
On Wednesday, Bush heralded the Senate version of the bill, arguing that it's better than the one that failed to pass the House 228-205 on Monday.
"It's very important for members to take this bill very seriously," Bush said while meeting with NATO Cmdr. Gen. McKiernan in the Oval Office. "It's very important for us to pass this piece of legislation so as to stabilize the situation, so that it doesn't get worse and that our fellow citizens lose wealth and work. ... the bill is different. It's been improved."
ABC News' Kate Barrett and Dean Norland contributed to this report.