The Shopping Center Group's Birnbrey said other challenges facing Uniqlo include finding the type of flagship locations the brand is used to for its off-mall locations (its Fifth Avenue store in New York is about 80,000 square feet) and balancing its physical footprint with its online presence.
"Every retailer is challenged by that," he said.
Forming an integrated shopping experience across online and in-store is another difficulty Uniqlo faces compared with its already established bricks-and-mortar competitors, Spiegelman said. Although many retailers are criticized for having store bases that are too large, these footprints give them an inherent advantage in that they can offer customers quicker distribution.
Meyer said Uniqlo is still in the early stages of developing its strategy for online and in-store, which currently operates through a distribution center on each coast.
Watching how this online strategy develops will ultimately determine how many stores the retailer opens in the U.S. market, Meyer said.
"The [store] mix that we will have in 2020 from where I sit today is different than the vision I had two years ago because of the growth of e-commerce," he said. "That combination will decide what the ultimate mix is."
Read MoreArt critic speaks out against Uniqlo, MoMA tie-up
Still, one positive for the brand's online presence was the reaction its website received in the wake of the announced store openings. Meyer said that the brand saw a noticeable uptick in traffic to the site coming from each market as it was announced.
Its growing virtual popularity was also underscored by recent research at Jefferies, which found the Uniqlo site posted the second-highest growth among specialty retailers in unique visitors in April compared with the prior year, with 315,000 visitors.
"The Uniqlo brand is beginning to demonstrate an ability to transcend Eastern and Western cultures, a unique and powerful characteristic often associated more with European or American brands," ISI analyst Omar Saad wrote in a note to investors.
—By CNBC's Krystina Gustafson.