Both won Friday and advanced to the final of the Miami Open, which moved this year to the Dolphins' complex from its longtime Key Biscayne home.
Federer dominated a semifinal battle of the ages, beating 19-year-old Canadian Denis Shapovalov 6-2, 6-4. Defending champion Isner also bested a Canadian teenager, 18-year-old qualifier Felix Auger-Aliassime, 7-6 (3), 7-6 (4).
Both finalists give the new tournament site a thumbs-up, partly because they've done so well the past week.
"The venue is absolutely fantastic," said Isner, a big football fan. "To play in the stadium — the Super Bowl will be here next year — it's pretty amazing."
The atmosphere was lively for both matches, and each time experience triumphed. The age gap with Shapovalov was the largest of the 37-year-old Federer's career, and he used a wide array of shotmaking to take control with two early breaks.
"It was a tactical match by me," Federer said. "I'm happy I was able to play with variations."
Seeded No. 4, Federer improved to 17-2 this year. He lost in this month's Indian Wells final to Dominic Thiem and now seeks his fourth Miami Open title.
Federer is 5-2 against Isner, but they haven't played each other since 2015.
Isner, now 33, won his only ATP Masters title a year ago on Key Biscayne.
"It's amazing — I said before the tournament the chances were I would not defend my title," Isner said. "I'm very, very happy."
The 6-foot-10 American hit 21 aces in the semifinal and has 98 in five tournament matches. Federer laughingly said he'll brace for a barrage.
"I know what to expect," Federer said. "On Sunday I'll be the goalie and try my very best."
The women's final Saturday will match No. 5 Karolina Pliskova of the Czech Republic against No. 12 Ashleigh Barty of Australia.
The largest stadium crowd of the tournament watched Federer deploy his full repertoire against Shapovalov. That included a lunging stab volley for a winner, a half-volley drop shot for another winner, and a nifty chipped return while Federer held the racket like a flag, strings in front of his face.
"He's got every shot mastered," said Shapovalov, who considers Federer his idol. "When he needs a shot, he's going to go for it and he's going to make it. I don't think he has any weaknesses."
Shapovalov will climb to a career-best No. 20 in the rankings despite his defeat.
"Denis is a great player," Federer said, "and he will be even better in the future."
Like Shapovalov, Auger-Aliassime came up short in a bid for his first ATP Masters 1000 final. He served for both sets, but Isner broke each time by taking advantage of double-faults, and then used his big serve to control the tiebreakers.
Nine of his 10 sets in the tournament have gone to a tiebreaker, and he has won each one. But Auger-Aliassime figured neither set should have gotten to that point.
"It's a chance you can't miss, serving two times for the set," he said. "Just terrible."
Auger-Aliassime, 5-0 previously against top 20 opponents, was the youngest male semifinalist in the tournament's 35-year history. He'll jump to a career-best No. 33 in next week's rankings.
But he'll need steadier play at pivotal moments to fulfill his potential as a future Grand Slam champion.
Isner lost serve for only the third time in the tournament to fall behind early. Auger-Aliassime served at 5-4 but double-faulted into the net three times, including on break point.
There was a repeat in the second set. Auger-Aliassime served at 5-3, double-faulted once and then hit a swinging volley into the net on break point.
The teenager blamed nerves.
"It's like I caught a virus or something," he said. "I couldn't put a second serve in anymore. That's just very tough to swallow."
Each lapse led to a tiebreaker, where Isner has been unbeatable of late after arriving at Miami with a modest 7-10 record in tiebreakers this year.
He finished strong against Auger-Aliassime, whacking three aces in the final tiebreaker, the last on a 140 mph serve that was his fastest of the match.
"I'm playing well," Isner said. "Keep it up and see what happens."