Artemis II mission plan is to send four astronauts in the first crewed Orion capsule into a lunar free return trajectory for a 10 day mission. The mission will include the first non-American, Canadian specifically, and likely the first woman to leave low earth orbit. Because of the hydrogen boil-off due to the increased time spent in a LEO parking orbit compared to Artemis I, the mission will use a multi-translunar injection (MTLI), or multiple departure burns to preform the translunar injection burn. The burn will be partially completed by the ICPS 2nd stage before being fully completed by the European Service Module (ESM) on the following orbit.

It was planned to include several cubesats in the adapter between Orion and the ICPS second stage, similar to Artemis I. However, no official announcement was ever made regarding these satellites, and it is unclear if they will be included.