Even before Graham Platner withdrew from Maine’s Senate race in disgrace this month, he and his Democratic allies were severely outmatched in the race for cash.

Now his expected replacement, Troy Jackson, inherits a difficult situation: He has just over four months to erect a defense against a towering Republican super PAC apparatus that is intent on re-electing Senator Susan Collins.

Ms. Collins is relying on a web of deep-pocketed outside groups, funded largely by billionaire megadonors, to spend tens of millions of dollars on advertising promoting her and attacking the Democratic nominee. Her campaign, her allies and other groups aligned with Senate Republican leadership have already reserved about $60 million in airtime through the fall, according to the media tracking firm AdImpact.

That is far more than the roughly $24 million that Senate Democrats’ main super PAC and its affiliates have allocated to ads in Maine, though more could be on the way.

With Republicans set to outspend Democrats that drastically, a bruising, asymmetrical battle is about to unfold for a seat that could be pivotal to control of the Senate.

“We’re probably never going to be able to match what the Republicans are going to spend, but we’ve got to have a fight,” said Rufus Gifford, a leading Democratic fund-raiser who hosted an event for donors to Mr. Platner in May. He added, “This is not a level playing field by any stretch of the imagination.”