Both players missed Tuesday's straightforward 2-0 victory over Stoke City through injury, but Ferguson expects both men to overcome their niggles in time for the trip to Stamford Bridge.
He is also hopeful Ashley Young will be available for selection, although the game may just come too soon for the former Aston Villa winger.
"We're hopeful Wayne Rooney, Nani and possibly Ashley Young will be fit for Sunday," Ferguson told MUTV.
Ferguson's biggest selection headache on Tuesday was in goal, as both Anders Lindegaard and David De Gea picked up injuries in the final training session before the game. Third-choice custodian Ben Amos was thus drafted in and dealt adequately with what little he was asked to do.
As a result, Ferguson suggested he may make a second Premier League start at the weekend.
"Anders got injured in training and then David got injured at the end of training, so we had a right nightmare there," he noted. "Ben Amos didn't have a lot to do but he was confident and he was composed. I'm pleased with that."
With United now level on points alongside Manchester City in the title race after Roberto Mancini's men lost to Everton, Ferguson refused to get carried away.
He noted: "It's still early doors [in terms of the title race]. It's only the last day in January. I always say that March is a very important month, as well as the beginning of April. We play Manchester City in April, for instance."