The Palazzo was developed by Las Vegas Sands as a sister property to its Venetian resort, opened in 1999.

The Venetian opened while construction was ongoing, and Adelson sought to wait for its completion before seeking financing for another resort.

[9][12][13] Zeldin declined numerous offers to purchase the Tam O'Shanter,[10] including one from businessman Howard Hughes.

[10][14] Before his death in 1997,[15] Zeldin finalized a $12.5 million deal to sell the Tam O'Shanter to Las Vegas Sands.

[19] The land had also been occupied by the Las Vegas Kosher Deli,[20] as well as several small stores owned by the Venetian that were expected to close, helping make way for the Palazzo.

[14] Local developer Steve Wynn opposed the project, alleging that the Venetian/Palazzo site already suffered from inadequate parking.

Crews spent 13 months excavating nearly 70 feet deep, in order to build a 4,400-space underground parking garage.

[26][27] In December 2004, Las Vegas Sands made its initial public offering, with some of the proceeds going toward the Palazzo project.

[42] Travelocity ranked it in eighth place in a 2011 list of top 10 Las Vegas hotels, based on guest reviews.

[64] The Palazzo also includes the Waterfall Atrium, which features seasonal decorations overseen by a team of gardeners, horticulturalists, and landscapers.

[65] The decorations are exhibited for free, and themes include Chinese New Year,[66][67][68] Fourth of July,[65] autumn,[69] and Christmas.

[70] In its first year, the atrium also hosted a free show, The Living Garden, which featured actors dressed as statues and grapevines.

[71] Rosina, a 65-seat lounge with an Art Deco design, opened in 2017,[72][73][74] as part of a two-year renovation which included the casino floor and hotel rooms.

Completed in 2018, the project included the addition of colored lighting on the casino's ceiling, and the new Electra Cocktail Lounge.

[75][76] The Palazzo initially featured more than a dozen restaurants,[36] from chefs such as Wolfgang Puck, Charlie Trotter, and Guy Savoy.

[86][87] Adelson had wanted the business opened sooner, blaming its developers for repeated delays brought on by redesigns.

He had terminated the nightclub's lease in March 2008, stating that the failure to open on time resulted in poor business for the resort.

[108] In November 2006, Las Vegas Sands sought approval from the Clark County Commission to construct a condominium tower on part of the Palazzo land.

[110] Both the retail building and tower were constructed on less than an acre of land, previously occupied by the Rosewood Grille restaurant.

[107][108] In November 2008, Las Vegas Sands indefinitely suspended construction due to the Great Recession.

"[117][119] Michael Leven, president of Las Vegas Sands, had a view of the unfinished tower from his third-floor office, and later said: "I couldn't stand looking at that steel.

"[119] In April 2014, Leven said that money was no longer an issue in completing the project, stating, "It's not a financial decision anymore, but we want to do the right thing," referring to the ultimate use of the building.

Because of uncertainty in the high-end, high-rise residential market, Leven stated that it was unlikely the tower would be completed as condominiums.

Up to that time, Las Vegas Sands had considered finishing and opening the tower as timeshares, but Leven stated that "the numbers didn't work out".