Last time around, Nate McMurray seemed to have everything going his way.

The man he was trying to unseat, Representative Chris Collins, was hit with federal insider trading charges three months before the 2018 general election. Mr. Collins, a Republican, temporarily suspended his campaign; even when he resumed, he raised little money and made few public appearances in the district in Western New York.

Despite those advantages, Mr. McMurray, a Democrat, fell short, losing by less than 1,100 votes. The result underscored Mr. McMurray’s challenge, then and now.

The 27th Congressional District is about as Republican as New York, a deep blue state, can get. Donald Trump carried the district by some 25 points in 2016, and Mr. Collins had been one of the president’s earliest and most ardent supporters.

But Mr. Collins’s tenure came to a screeching halt last fall, when he resigned and pleaded guilty, creating a vacancy that will be filled by a special election on Tuesday.

Mr. McMurray is back to try again — and will face state senator Chris Jacobs, the Republican candidate, in a race that is potentially a harbinger of the electoral mood ahead of November’s presidential election.