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CHICAGO - Mitt Romney's been here before. Combating an upstart opponent with lots of momentum. Facing questions about his inability to seal the deal. Heading to a state he could easily lose.

After Rick Santorum ran off a streak of surprising victories in Minnesota and Colorado, Romney desperately needed a win in Michigan. With Santorum set to take key Super Tuesday states like Tennessee and Oklahoma, Romney desperately needed a triumph in Ohio.

Both times Romney came through. Two crucial Midwestern states, two nail-biter victories. Now the frontrunner in the Republican presidential primary will have to do so yet again in Illinois. Once again, Santorum is surging, winning in both Alabama and Mississippi on Tuesday. Once again, Romney is trying to fend off questions about his failure to secure the nomination after half the states in the country have already voted. And once again, Romney is going into a state that will not be easy for him to win.

Make no mistake - Romney is the favorite in Illinois. The former Massachusetts governor enjoys strong support in the Chicago area, the backing of the state's GOP establishment, including Sen. Mark Kirk and Illinois Republican Party chairman Pat Brady, and a big financial advantage over Santorum. Romney's campaign is buying up nearly $1 million worth of airtime in the state, while his super PAC - Restore Our Future - has already shelled out over $900,000, according to Federal Election Commission filings. In addition, the super PAC has bought another $1.5 million of TV time in the past week alone. Santorum, by comparison, is only set to go on the air Thursday with a $116,000 ad buy.

The importance of success in Illinois is clearly not lost on Romney or his campaign. On Wednesday afternoon Romney held a tele-town hall event with voters here. The GOP hopeful is reportedly planning to spend primary night in Illinois, arriving next Monday and sending half a dozen staffers ahead of time. When the state votes next Tuesday, 69 delegates will be up for grabs, more than in Ohio and Florida. Victory for Romney here could help stop Santorum's momentum and reassert his position as the overwhelming favorite to win the nomination. While Romney still has a massive lead in the delegate count - 496 to Santorum's 252 - he has thus far failed to put away his key rival, a candidate who - despite the odds - continues to score one upset victory after another.

On Tuesday Santorum won the primaries in Alabama and Mississippi, with half the voters in those states saying that Romney was "not conservative enough." The former Pennsylvania senator, meanwhile, enjoyed very broad support among voters looking for the "true conservative" in the race. It was only the latest sign of unrest among Republican voters about Romney's conservative credentials.

With Romney spending serious cash in the Chicago market and expected to enjoy a clear advantage over Santorum in the area, Santorum's best chance at winning Illinois will likely depend on success downstate. In the primary thus far Santorum has done well in the Midwest overall - Michigan and Ohio aside - and more specifically, in rural areas. Romney's victories in Michigan - his native state - and Ohio earlier this year, for instance, have stemmed from his advantages in the Detroit area and cities like Cleveland and Cincinnati. Illinois is now shaping up as a similar battle between the two sides.

One wild-card factor is former House Speaker Newt Gingrich, who continues to disregard calls to drop out of the race even though he has only won two of the first 25 states to vote - his native state of Georgia, and the neighboring state of South Carolina.  After calling Alabama and Mississippi "must-win" states, Gingrich then slumped to second-place finishes in both, but still refused to quit.

However, Gingrich may find it difficult to get any momentum going forward. At Gingrich's first campaign stop in Rosemont, Illinois on Wednesday, only around 40 people showed up - the number of reporters virtually equaled the number of audience members. While Gingrich has virtually no chance of winning the nomination, his continued presence in the race is a factor for both Romney and Santorum, since he competes for the same type of conservative voters that Santorum is courting. Simply put, the longer Gingrich stays in the race, the more it helps Romney.

Another factor hurting Santorum is a paperwork issue that will affect his ability to pick up delegates here. His campaign did not file a full slate of delegates, so Santorum will not be able to pick up any delegates in four of the state's 18 Congressional districts. That type of snafu already hurt his cause in Ohio earlier this month.

One potential advantage for Santorum, however, is that Illinois will have special interest to the campaign of President Obama, which has been attacking Romney relentlessly for months. Obama, of course, was an Illinois Senator before he won the White House in 2008 and his campaign headquarters is based in Chicago. Rest assured that the Obama campaign will be doing everything in its power to damage Romney's chances in Illinois - in the hope of not only damaging Romney ahead of a likely general election showdown come this fall, but also prolonging the Republican primary as much as possible. If Romney's much-needed triumph in Michigan was made possible in part by playing on his own home turf, the Illinois primary will not only be an away game, but one played in Obama's back yard. The president, in fact, will be in Chicago this Friday on a fundraising trip, only days before Romney and Santorum square off for the chance to oppose him in November.

With his huge lead in the delegate count, Romney remains the overwhelming favorite to earn that chance. Despite losing in Alabama and Mississippi on Tuesday, Romney managed to win more delegates than Santorum on the day - 41 to 35 - thanks to his victories in Hawaii and American Samoa. But once again, Romney now finds himself trying to knock off an upstart opponent, with all the momentum, in a tricky state. While it is a position he has been in before - and come out of on top - Illinois is only the latest firewall for Romney in an unpredictable campaign that has already lasted longer than he had hoped. The pressure-packed primary will be familiar for Romney after his battles in Michigan and Ohio. The question is, will the result be, too?

Matthew Jaffe is covering the 2012 campaign for ABC News and Univision.