After Wanderers youngster Atiya Waraga had a 59th-minute strike ruled out for offside, the Victory's Brazilian winger Santos scored a terrific solo goal in the 71st, before Nikos Vergos sealed it in added time.
Superstar Juan Mata returned from a fractured elbow in the 82nd minute to give Arthur Diles's charges a pre-finals boost.
While the win temporarily lifts the Victory (40) to third, they are guaranteed to drop to at least fourth as Adelaide United (40) and Melbourne City (38) play on Sunday, when Sydney FC (38) face Auckland FC (41).
"We knew we couldn't get third spot but we wanted a home final," Diles told Paramount Plus.
"We've done everything we can and now it's up to the football gods."
The Victory were never in contention to claim the newly-opened play-off spot handed to Australia for the Asian Champions League Elite overnight on Friday.
The second-highest Australian team behind premiers Newcastle - one of Adelaide, Sydney or City will earn it.
Melbourne were second best for much of Saturday night's contest at CommBank Stadium, with goalkeeper Jack Warshawsky keeping the Wanderers at bay.
Western Sydney thought they had claimed a deserved lead in their season closer when Bozhidar Kraev's super ball to the back post hit Borrello - who was jostling with Jason Davidson - and fell to Waraga to score.
But Waraga was ruled offside after a VAR check, denying the 19-year-old a maiden goal.
"It looked pretty inconclusive from my perspective," interim coach Gary van Egmond told Paramount Plus.
"But we've had a number of those ones this year.
"So if it could go wrong, it has gone wrong, unfortunately, and hopefully we've used up all of the bad luck this year so that next year we'll have better luck."
It was van Egmond's final game, with Ufuk Talay taking over next season.
The Victory scored after a Western Sydney corner, with Santos pinching the ball away from Angus Thurgate and bursting down the right before finishing with a fierce strike.
The hosts' Ryan Fraser and Dylan Scicluna both hit the woodwork in the 85th minute, while Victory defender Brendan Hamill returned from an ACL tear late before Keegan Jelacic teed up Vergos to score a deflected goal in the 92nd minute.