Liberal groups have made Toomey one of their prime targets in the search for that last tally. His hometown congressman, Republican Charlie Dent of the Lehigh Valley, has cosponsored the House version.
Toomey is undecided, a spokeswoman said Friday.
State Rep. Brian Sims, a gay Philadelphia Democrat, wrote Toomey an open letter Friday urging him to support the bill, saying it would give gays, lesbians, bisexuals, and transgendered individuals the same protections as other groups.
"I believe that there is no single piece of civil rights legislation in existence that is more impactful to members of the LGBT community than a fully inclusive ENDA," wrote Sims, who was the first openly gay candidate to win a seat in Harrisburg. "No one should lose their job, be subjected to discriminatory treatment or harassment, or be denied the opportunity for advancement because of bigotry, fear or hatred."
For Toomey, who prefers to focus on fiscal issues, the vote could either reinforce his conservative credentials, or appeal to crucial moderates.
On Friday, Heritage Action, the political arm of the conservative Heritage Foundation, urged senators to vote no. The group warned that the bill would force business owners to "adopt the government's values" and "severely undermine civil liberties, increase government interference in the labor market, and trample on religious liberty."
Heritage Action also questioned whether the religious protections in the bill were sufficient and warned that it would create "special privileges."
On the left, MoveOn.org has targeted six Republicans, including Toomey, to try to persuade them to support the measure. A coalition of civil rights groups, labor unions, and gay-rights organizations delivered more than 4,100 postcards to Toomey's Harrisburg office last week pushing for his vote.
The region's Democratic senators - Bob Casey of Pennsylvania and Bob Menendez and newcomer Cory Booker of New Jersey - support the bill, and have not faced the same kind of pressure.
Toomey is conservative on most social issues but has usually been careful to stick to fiscal concerns and avoid the cultural battles waged by some other Republicans, such as former Pennsylvania Sen. Rick Santorum.
To be sure, the bill has almost no chance in the GOP-controlled House. But the Senate vote will put Toomey and other Republicans from moderate states on the spot, providing potential campaign fodder for Democrats.
The measure moved to the brink of Senate approval after gaining backing from moderate Democrats - including Joe Manchin of West Virginia, Toomey's partner on a gun background-check bill last spring.
Pennsylvania appears to be moving toward stronger support for gay rights. A Franklin and Marshall College poll in May found that 53 percent of registered voters favored same-sex marriage; 43 percent opposed the idea.
That was an 11-point swing in favor of marriage equality from 11 months earlier.
Toomey has said he believes marriage is between a man and a woman.