La Roja beat Norway 2-1 on Saturday to open their qualification campaign with a victory, but Malta will be full of confidence following their 2-1 home success over the Faroe Islands.
Malta will be the huge underdogs on Tuesday night, but Ray Farrugia's side will be feeling extremely good about themselves following a 2-1 victory over the Faroe Islands at the weekend.
Indeed, the win proved to be Malta's first in a home competitive match for almost 13 years. Not since a 2-1 success against Hungary in October 2006 had the Reds managed to triumph in a competitive fixture on their own patch, but that long unwanted record ended in Ta'Qali against the Group F minnows.
Malta have competed in every qualifier for the European Championships and World Cup, but have never managed to make it to the finals of any major international competition. Before Saturday's win over the Faroe Islands, they had not won an international fixture since beating Ukraine in a friendly back in June 2017.
To be blunt, they are not a team used to winning matches. All but one of their current squad plays their football in the Maltese league, with the only exception being Zach Muscat, who turns out for Olhanense in Portugal.
They are still led by former Coventry City forward Michael Mifsud, who has 41 goals in 137 appearances for his national team. Currently with Birkirkara, the 37-year-old was joined in attack by Nwoko at the weekend, and as mentioned, the Valletta forward managed to register his first international goal.
In terms of what is ahead for Malta - after facing Spain they will travel to Sweden for their next Euro 2020 qualifier on June 7, before hosting Romania four days later. It seems incredibly unlikely that Farrugia's side will be able to challenge for a spot high up the section, but they will be keen to give a good account of themselves on Tuesday.
Recent form: W
Recent form (all competitions): DLDLDW
Spain ensured that they would open their Group F qualification campaign with a victory as they recorded a 2-1 success over Norway at the Mestalla on Saturday. Sergio Ramos's 71st-minute penalty proved to be the winning goal, but it was far from a convincing performance from Luis Enrique's side.
No longer able to call upon the likes of Andres Iniesta, David Silva and Gerard Pique, it is very much a different era for Spain. There is still plenty of talent in the squad, but they are a team very much going through a transitional period.
There does seem to be an issue when it comes to the attack, with Alvaro Morata, Rodrigo, Marco Asensio, Jaime Mata and Iker Muniain only boasting 19 international goals between them. Morata has 13 of those, but he has not exactly had the best of campaigns at club level.
It has been a disappointing few years for Spain; they exited the 2014 World Cup in the group stage before being knocked out of last year's World Cup in the round of 16. La Roja are three-time winners of the European Championships - including back-to-back titles in 2008 and 2012 - but they were eliminated from the 2016 competition in the round of 16.
Spain have won each of their last four away European Championship qualifiers, though, with their last defeat on the road coming against Slovakia in October 2014. Home and away, La Roja have been victorious in their last nine European Championship qualifiers and will fancy their chances of making it 10 in a row against Malta.
Enrique's side will then travel to the Faroe Islands in their next qualifier on June 7, before welcoming Sweden and travelling to Romania in their next two. It is not the most difficult of groups, but there is no question that Sweden have the credentials to cause Spain issues, as Norway did on Saturday night.
A win, with a clean sheet and plenty of goals, will be the order of the day for Spain, and they are certainly capable of running up a score, having put four past Wales and six past Croatia in the latter stages of 2018.
Recent form: W
Recent form (all competitions): WWLLWW
Malta will be without their most experienced defender on Tuesday night through suspension, with Andrei Agius receiving a red card against the Faroe Islands at the weekend.
Zach Muscat for Agius could be the only alteration, although there have been suggestions that Farrugia could switch to a back five, allowing Joseph Zerafa to come into the XI.
Mifsud and Nwoko, however, will both keep their positions in the final third of the field.
As for Spain, Enrique would not have been convinced by what he saw against Norway, which could lead to changes.
Muniain and Mata are also under consideration to start as part of a front three.
Malta possible starting lineup:
Bonello; Zerafa, Caruana, Muscat, Borg, Mbong; Nwoko, Guillaumier, Fenech, Corbalan; Mifsud
Spain possible starting lineup:
De Gea; Roberto, Ramos, Inigo, Alba; Ceballos, Saul, Canales; Rodrigo, Morata, Muniain
Head To Head
Tuesday night will be the eighth international meeting between the two teams. Spain have won each of the previous seven, including a 4-0 victory when they last locked horns in February 1997.
Spain's biggest victory over Malta was a 12-1 home success in December 1983, while La Roja have won 3-2, 2-0 and 3-0 on their travels.
We say: Malta 0-4 Spain
It is very difficult to predict anything other than a comfortable Spain victory. Enrique's side were not exactly brilliant against Norway, but they will have too much for Malta, despite the home team's new-found confidence.