The Paraguay international spent a season on loan at Betis from Manchester City two years ago and wants to put on a winning performance not only for his own personal benefit but to stop the rot for Malaga.
Los Boquerones are winless in their last five Primera Division games and Santa Cruz does not expect an easy ride in the Andalusian derby.
"Playing against your former team always makes for a special match. We're really looking forward to playing at home on Sunday and giving our fans a long-awaited win," the 32-year-old told the club's official website.
"Betis aren't going to change their style of play or their philosophy for this game.
"We'll be up against the same strong team they've always been, and although we're expecting a difficult match this weekend, we're prepared to win.
"It's vital that we concentrate on our job on Sunday. It's going to be a classic derby match and we're confident we can keep the three points at La Rosaleda."
Malaga's last league win came at home against Almeria on September 24 while Betis also have to look back as far for their most recent win, a 1-0 victory over Villarreal five days after their local rivals.
Despite their stuttering form, Santa Cruz believes home advantage could be the key to unlock a win against their fellow strugglers.
He said: "We've got the added bonus of our fans' support at our home ground.
"Their loyalty to us is really second to none, so we're hoping to reward them with a win."
Betis boss Pepe Mel revealed he will be without several players for the clash.
He said: "Paulao will not be available. Perquis is very doubtful until tomorrow. Amaya, Guille Sara and Ruben Castro are dropped. Lolo, Salva and Nosa will not be there either."