World number five Zverev, also Foro Italico champion in 2017, comfortably won his sixth Masters 1000 title by beating Nicolas Jarry 6-4, 7-5 and is eyeing glory at the Paris clay-court Grand Slam, which gets underway next weekend.
In front of a packed centre court crowd Swiatek won her 36th match of the year and became the first woman since Serena Williams in 2013 to win at Madrid and Rome in the same season.
Iga Swiatek swept past Coco Gauff to reach the Rome Open final on Thursday where Aryna Sabalenka will stand in her way of a third title and her bid to match a Serena Williams record.
Djokovic said that his subdued performance on a court where he has won six titles might have been due to the blow suffered while greeting fans on Friday night.
Djokovic's bid for a record-extending 41st Masters 1000 title was ended in just over an hour by Chilean Tabilo, who is ranked 32nd in the world but was hugely impressive and claimed his first win over a top-10 opponent.
Defeat to seventh seed Hurkacz casts doubt over whether clay-court icon Nadal will play at the upcoming French Open, where he has won a record 14 titles.
Novak Djokovic was left in agony after being struck with a hard plastic water bottle as he left the court following his 6-3, 6-1 win over France's Corentin Moutet at the Rome Open which advanced him to the third round on Friday.
"I have Roland Garros in just two weeks and a half... I need to prove myself if I am able to push my body to the limit, I need to push to feel myself ready for what's coming," Nadal told reporters.
World number one Novak Djokovic said he believes he will be in top form for the French Open and hopes to prove that at the Italian Open which started on Wednesday.
The 22-time Grand Slam singles champion has recently returned to the circuit after a long absence due to injury.
Rublev, who takes the Madrid crown from double champion Carlos Alcaraz whom he beat in the quarter-finals, said he had played despite feeling ill at times this week and hailed his doctors for helping him through.
Coming back from 1-3 down in the decider and saving three match points in total, Swiatek claimed a 7-5, 4-6, 7-6 (9/7) victory to secure the Madrid Open trophy for the first time.
Rublev upset home favourite Alcaraz 4-6, 6-3, 6-2 to reach the semi-finals.
Last month, the Serb ended a five-year partnership with coach Goran Ivanisevic.
Spaniard Carlos Alcaraz says he will form a dream team with his legendary compatriot Rafael Nadal in the men's doubles at the Paris Olympics later this year "if everything goes well."
On the women's side, Iga Swiatek was made to sweat in her 4-6, 6-0, 6-2 victory over Brazilian lefty Beatriz Haddad Maia, as she dropped her first set of the tournament and needed two and a half hours to reach a second consecutive Madrid semi-final.
"Now I'm enjoying. Let's see how I wake up tomorrow. Playing at home means everything to me, just try my best to keep dreaming."
Nadal's reward is a last-16 clash with the 30th-seeded Jiri Lehecka on Tuesday.