The Liverpool striker has been in exceptional form for La Celeste over the last eight months, scoring 10 goals in his last eight international appearances, including two strikes in three group-stage outings at the Copa America.
Nunez, who is just two goals behind Argentina's Lautaro Martinez (four) in the race for the Golden Boot, is expected to lead the line once again at the expense of veteran striker Luis Suarez, with support set to be provided in attack by Facundo Pellistri and Nicolas de la Cruz.
After watching his side win all three games in Group C to qualify for the knockout rounds in first place, scoring nine goals and conceding only one in the process, head coach Marcelo Bielsa is unlikely to make too many change to his starting lineup.
However, he could be forced to make at least one alteration after Maximiliano Araujo was stretchered off wearing a neck brace following a nasty collision in Uruguay's 1-0 win over USA on Tuesday; Cristian Olivera could be the man to deputise on the left flank.
Captain Federico Valverde and in-demand Manuel Ugarte should continue to link arms in the middle of the pitch, meaning Rodrigo Bentancur will be forced to watch on as a substitute to begin with.
Mathias Olivera scored the only goal in Uruguay's win over USA and he is expected to retain his centre-back spot next to Barcelona's Ronald Araujo, while Nahitan Nandez and Matias Vina should continue as full-backs.
Uruguay possible starting lineup: Rochet; Nandez, R. Araujo, M. Olivera, Vina; Ugarte, Valverde; Pellistri, De la Cruz, C. Olivera; Nunez