Battle of the big spenders: Will City's investment secure Champions League glory?
While City remain novices at the top level in Europe, Real are in the last four for a record 27th time and are bidding to reach their 14th final.
City's turnaround in fortunes since the late 1990s has seen the club transformed from perennial underachievers into one of the major players in European football.
Since winning the Football League Second Division playoff final in 1999, the club has undergone a remarkable resurgence.
City have spent almost $1.4 billion on players in the last 17 years in their quest to establish themselves as a European powerhouse.
The takeover in 2008 by Sheikh Mansour, a ruling member of the Abu Dhabi royal family, accelerated City's rise up the ranks, with the club going on to claim its first league title in 44 years in 2012.
Their progress in Europe has come at a significant price, with the club spending $520 million on players since that title win.
In comparison, Real have spent $456m during the same period, although it's worth noting their total outlay since 1999 has been an eye-watering $1.75bn.
It could be argued that Real's 'Galacticos' spending policy hasn't really delivered the results the club would have expected, with just five domestic titles and three Champions League titles to their name since 1999.
City added another Premier League title to their record in 2013/14, but they are hoping their spending will secure success at Europe's highest level.
Real have reached the semi-final stage for the past five years, with their only success coming in 2013/14, when they defeated Bayern Munich before going on to claim their 10th title by beating Madrid rivals Atletico in the final.
The two teams' only previous Champions League meetings came in the 2012/13 group stage, with Real winning 3-2 at home before securing a 1-1 draw in Manchester.
Both progressed to the semi-final this season courtesy of 3-2 aggregate victories – City beat Paris St-Germain, while Real knocked out Wolfsburg.
City have won three and drawn one of their Champions League home games this season, and they have the same record away from the Etihad.
Real boast a perfect record at the Bernabeu, winning all five games without conceding a goal. Away from home they have won three and drawn one, with their only defeat coming at Wolfsburg in the last round.
Their 2-1 loss at Juventus in last season's semi-final first leg is the only other defeat in their last 12 European away games, with eight wins during that time.
Both teams go into the game in excellent form, with City unbeaten in seven games in all competitions while Real have reeled off five straight victories since the Wolfsburg loss.
Manuel Pellegrini will be desperate to end his time as City manager with the Champions League trophy to his name, but with Real winning on their last three trips to England and a formidable home record to fall back on, they are big favorites to reach the final in Milan.