The Malaga striker is Paraguay’s all-time leading goalscorer and will be confident of adding to his tally of 29 goals against the Emiratis at Stadion Villach in Austria.
The match will be the South American side's first hitout since they drew 1-1 against France in June after they pulled out of their friendly against Ukraine this week due to safety reasons.
Coach Víctor Genes has picked a fairly inexperienced squad to travel to Austria, with just four players out the 19 selected with more than 10 caps to their name.
Defender Jose Caceres and midfielder Miguel Paniagua could be in line to make their debuts for Los Guaranies against the world’s 65th ranked team, while Santa Cruz’s three fellow strikers have just seven caps between them.
While on paper it may seem like the Paraguayans will cruise to victory, they would do well to not underestimate a young UAE side who are set to turn some heads at the upcoming Asian Cup in Australia.
Coach Mahdi Ali's men have recently played out two draws against European opposition, holding Norway to a 0-0 stalemate last week before Abdulaziz Sanqour scored a last-gasp equaliser in their 1-1 draw with Lithunia on Wednesday.
With a team stacked full of Al Ain players who recently qualified for the semi-finals of the AFC Champions League after an impressive win over Saudi Arabian side Al Ittihad, the UAE have enough pace to trouble the Paraguyan defence.
They will be without captain Ismail Matar however, with the 31-year-old still recovering from a knee injury that has kept him out of his side's European tour.
The match will be the first meeting between the two nations and will be an important hitout for the UAE has they continue their preparation for the Asian Cup.
