While the Toffees have historically had the edge over City, in more recent seasons, the Foxes have enjoyed success against the Merseyside outfit, both at home and away.
Ahead of the 115th competitive encounter between the two clubs, LCFC.com takes a closer look at Everton's manager, squad, trophy cabinet and more...
The manager
Italian legend Carlo Ancelotti signed a four-and-a-half-year deal at Everton on 21 December, 2019, replacing Marco Silva at Goodison Park, following Duncan Ferguson's brief spell as caretaker manager.
As a midfielder, Ancelotti enjoyed a successful career during his playing days, winning the Serie A title once with AS Roma and on two occasions for AC Milan, alongside four Coppa Italia triumphs in Rome.
In 1989 and 1990, Reggiolo-born Ancelotti also lifted two European Cups with Milan, while finishing third at the FIFA World Cup, in his homeland Italy, in 1990.
He initially started his coaching career as Italy's assistant manager, alongside Arrigo Sacchi, before guiding Serie B side Reggiana to promotion to the top tier in 1996 and leaving after one season.
His next move was to Parma, where he oversaw a side including Gianluigi Buffon, Fabio Cannavaro and Gianfranco Zola, who helped him to seal a second-placed finish in his first season.
A disappointing sixth-placed standing in 1997/98, though, ended with him departing and moving onto Juventus in February 1999, where he both succeeded and preceded another legendary Italian manager, Marcello Lippi.
Despite holding a five-point lead in the title race with three games to go in 1999/00, Lazio pipped Juventus to top-spot, and Ancelotti left after another second-placed finish in 2000/01.
The Italian's eight-year spell at Milan, though, is regarded as his most successful stint, winning Serie A in 2004, the Coppa Italia (2003), UEFA Super Cup (2003 and 2007), Supercoppa Italiana (2004), FIFA Club World Cup (2007) and two UEFA Champions League titles, in 2003 and 2007.
A move to England to manage Chelsea in 2009 resulted in the Premier League title during his first season, scoring 103 goals in the process, which was added to by the FA Cup, beating Portsmouth at Wembley.
Ancelotti headed to Paris Saint-Germain in 2011, lifting Ligue 1 in 2013, before, at Real Madrid, also securing a third Champions League, the Copa del Rey, Super Cup and FIFA Club World Cup.
One year as Bayern Munich's manager, on the other hand, replacing Pep Guardiola, resulted in the 2016/17 Bundesliga title, as well as two DFL-Supercup successes, before an unusually trophy-less spell at Napoli.
The squad
A squad already boasting a plethora of international players, including England goalkeeper Jordan Pickford, Brazil star Richarlison and Iceland playmaker Gylfi Sigurðsson, was significantly strengthened in the summer.
In came defensive midfielder Allan, from Napoli, for a reported £22M, while £20M was reportedly spent on Watford's central midfielder Abdoulaye Doucouré, and a similar fee was said to have been outlaid on Norwich City centre-back Ben Godfrey.
Former Real Madrid attacking midfielder James Rodríguez, on the other hand, also joined the Toffees on a free transfer from the Spanish giants as Carlo Ancelotti added yet more international pedigree to his squad.
However, headlines have been stolen in 2020/21 so far by the talents of Sheffield-born striker Dominic Calvert-Lewin, who has already notched 15 goals in all competitions for Everton.
While Calvert-Lewin is the Toffees' top scorer, goals have been hard to come by in other areas, with Richarlison (6) their next most prolific marksman, ahead of Keane (4) and Rodríguez (3).
Long-time Toffee Séamus Coleman remains club captain at Goodison Park, with Sigurðsson and Lucas Digne deputising, while Theo Walcott (Southampton) and Moise Kean (Paris Saint-Germain) are out on loan.
Previous encounters
Everton have the upper hand in the all time head-to-head record between the two clubs, winning 44 of their past encounters, while City have triumphed on 38 occasions, with 32 draws.
Last time out, meanwhile, the Toffees left King Power Stadium with a 2-0 victory on 16 December, 2020, with Richarlison and Mason Holgate finding the net in City's most recent competitive defeat.
Since the Club moved to King Power Stadium, however, City have tasted victory on three occasions, including a 3-1 success over Roberto Martínez's men on the day they lifted the Premier League trophy in 2016.
Form guide
Everton head into Wednesday's fixture on the back of three consecutive victories in all competitions, most recently enjoying a 3-0 success over Sheffield Wednesday in the Emirates FA Cup.
That victory, on Sunday, was preceded by an impressive 2-1 triumph at Wolverhampton Wanderers and a 2-1 home win over Rotherham United in the Emirates FA Cup.
While the Toffees have suffered losses to Manchester United, in the Carabao Cup, and West Ham United, in the Premier League, results since their visit to Leicester in December have been generally positive.
That run included victories over Arsenal and Sheffield United in the top flight, leaving Carlo Ancelotti's men well placed in the standings, two points adrift of fourth-placed Liverpool, with two extra games still to be contested.
The trophy cabinet
The Toffees have lifted England’s first division title on nine occasions, in 1891, 1915, 1928, 1932, 1939, 1963, 1970, 1985 and 1987, making them the top-flight's fourth most successful club.
Their trophy cabinet also features five FA Cups, of which their 1995 triumph is their most recent piece of silverware.
In addition, they won the second division in 1931, as well as the FA Community Shield (former FA Charity Shield) on nine occasions.
On the European front, meanwhile, a 3-1 victory over Rapid Vienna in Rotterdam saw them claim the 1985 European Cup Winners' Cup trophy.
The stadium
Goodison Park - affectionally nicknamed 'The Grand Old Lady' - has been the home of Everton Football Club since 1892, and has a capacity of just over 39,000.
Largely due to the Toffees' excellent league record over the years, Goodison Park has also hosted more top flight games than any other stadium in England.
The stadium’s record attendance came during the 1948 Merseyside derby, as over 78,000 fans watched Everton draw 1-1 with Liverpool.
Goodison Park has hosted an FA Cup Final, as well as a number of international matches, most notably a semi-final fixture at the 1966 FIFA World Cup.
With the unique St. Luke's Church protruding onto the site, between the Goodison Road Stand and the Gwladys Street Stand, the home of Everton FC is one of the most distinctive grounds in the Premier League.
However, the Merseyside outfit have recently began work towards building a new stadium at Bramley Moore Dock, on the banks of the River Mersey.
The reported £500M project will involve a 52,000-capacity state-of-art venue, which Everton say will generate a £1B boost to the local economy.
Upcoming fixtures
Following Wednesday's clash with Leicester, the Toffees welcome Newcastle United to Goodison Park in the Premier League on Saturday (12:30pm kick-off).
Then, Leeds United are the hosts as Everton head to Yorkshire to tackle Marcelo Bielsa's men on 3 February (7:30pm kick-off), before an away trip to Manchester United on 8 February (8pm kick-off).
All times GMT.