The teams convene in Prague at the start of a busy June schedule, with the hosts targeting a fast start in League A Group B, and their visitors preparing to compete on the global stage later this year.
After two campaigns in the Nations League's second tier, League B, the Czech Republic will compete at the highest level of Europe's newest international competition this time around.
The Czechs secured promotion by winning four of their six fixtures in the 2020 edition, and they now have a chance to compete alongside continental heavyweights Portugal and Spain, as well as Thursday night's opponents.
Set to face both Iberian counterparts in the coming fortnight - including games at home and away to La Roja - Jaroslav Silhavy's side return to competitive action after enduring a painful conclusion to World Cup qualifying.
Finishing only third in their group behind Belgium and Wales, they still advanced to the playoffs due to previous achievements in the Nations League, but were then beaten by Sweden deep into extra time.
Despite that significant setback, recent progress - including a quarter-final appearance at Euro 2020 - saw Silhavy renew his contract last month, and he now leads his side into a new era.
The prestige of sparring with some of Europe's top teams should spur on a squad that drew 1-1 with Wales in their most recent outing, even if several men from that get-together are absent this summer.
Semi-finalists in the inaugural Nations League back in 2019, Switzerland were less successful in their following campaign, amid tough competition at League A level.
Finishing third behind Spain and Germany still represented a respectable showing in 2020, but the Nati won just one of their six matches in a group also featuring Ukraine.
Ever since, though, they have gone from strength to strength, and a seamless transition has taken place from the much-lauded management of previous coach Vladimir Petkovic - under whom Switzerland famously knocked out neighbours France at Euro 2020 - to that of former international defender Murat Yakin.
The latter steered the Swiss through their World Cup qualifying campaign unbeaten, with five wins and three draws. Scoring 15 goals and conceding only twice, they upset European champions Italy to top Group C and reach the finals directly.
Though this summer now provides an opportunity to tackle some of their toughest rivals - following friendlies against England and Kosovo during the spring - Yakin has outlined his primary goal is to maintain rhythm ahead of November's trip to Qatar.
As star striker Patrik Schick is sidelined once again - having also missed the World Cup playoff defeat with a calf injury - the Czech Republic attack will be short of a proven threat ahead of their League A debut.
The three forwards named in Jaroslav Silhavy's squad for the upcoming quartet of fixtures have registered only one international goal between them, with Lokomotiv Moscow's Jan Kuchta likely to lead the line on Thursday despite having failed to break his duck in six previous appearances.
Verona playmaker Antonin Barak is also out of action, and Burnley striker Matej Vydra suffered a serious knee injury last month. However, the hosts' West Ham duo Tomas Soucek and Vladimir Coufal are available to start in midfield and at right-back respectively.
While Juventus midfielder Denis Zakaria has again been omitted by Murat Yakin, his former Borussia Monchengladbach teammate Breel Embolo enjoyed a strong finish to the Bundesliga season: finding the net in six of his last eight club appearances.
The latter led the line against England back in March - scoring the opening goal - and will compete with Haris Seferovic to start up front in a probable 4-2-3-1 formation.
Czech Republic possible starting lineup:
Vaclik; Zima, Brabec, Petrasek; Coufal, Lingr, Soucek, Kalvach, Jankto; Hlozek, Kuchta
Switzerland possible starting lineup:
Sommer; Widmer, Akanji, Elvedi, Rodriguez; Freuler, Xhaka; Steffen, Shaqiri, Vargas; Embolo
We say: Czech Republic 0-1 Switzerland
Lacking some craft and quality in the absence of both Barak and Schick, the Czechs are not best equipped to take the step-up in class at the moment, and may find adjusting to life in League A particularly challenging.
Now acknowledged as one of Europe's top footballing nations, Switzerland can therefore make their better attacking options pay - getting their latest Nations League campaign off to a successful start.
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