For some time, it was speculated that Austrian airline pilot Johanna Maislinger would take one of the two spaceflight participant seats, but on 13 May 2021, Space Adventures confirmed that Japanese art collector Yusaku Maezawa had acquired both seats, one for himself, with the other being taken by his production assistant, Yozo Hirano. This is the first time that two Japanese space fliers are launched together.

In July 2021, Space Adventures Moscow Office changed their previous story and said that Maislinger had never had access to the funds she had claimed, and they had never treated her as a serious candidate.

It was also reported for a time that Japanese entertainer Yumi Matsutoya was to fly on this space flight.

This flight also marks a departure from the traditional way space tourism has been done. On previous flights, the space tourist's mission would take place during either a "taxi" flight, where Soyuz lifeboats on the ISS were being swapped, allowing for a week or so-long mission, or during handover periods between crews, where the space tourist would launch with an incoming long-duration crew and land with the outgoing long-duration crew. Soyuz MS-20 is a departure from this model, as it involves a flight entirely dedicated to space tourism. American company Axiom Space also has a deal for a similar flight with SpaceX, where an Axiom-hired professional astronaut will fly with three paying space tourists to the ISS on board a SpaceX Dragon 2 spacecraft, scheduled for February 2022.