During the ISS4Mars workshops in 2020–2021, personnel from the International Space Station (ISS) partner agencies convened to reflect on scenarios for how the ISS could be used and its operations possibly modified to simulate aspects of a human mission to Mars. Scientific leaders, operations experts, crewmembers, managers, and flight surgeons discussed the five hazards of human spaceflight—gravity transitions, radiation, isolation and confinement, distance from Earth, and hostile closed environments—and considered how an ISS-based analog of Mars transit could benefit assessments and mitigations of these hazards. A focused writing team then discussed the advantages and disadvantages of each approach identified by the workshop participants before developing a set of eight use cases to consider the feasibility of implementing on the ISS. The writing team also identified the prerequisites needed, including ground analog studies simulating a mission to Mars required to verify measurements and procedures, before testing could begin on the ISS. Five of the use cases were considered feasible to assess in simulations using an ISS-based analog of Mars transit if some ground rules and assumptions were met. These five use cases were Earth-independent medical operations, Earth-independent integrated operations, life support and food for a one year duration, lower-body negative pressure as a countermeasure against the effects of exposure to microgravity, and fitness levels after landing. In addition, three more extensive interventions—extended Mars surface operations, a small-volume transit analog, and artificial gravity—were deemed unfeasible for testing on the ISS. Experience gained from the five use cases executed on the ISS may help answer some of the questions in the deferred scenarios, or it may be possible to complete them on another platform (e.g. commercial space station, lunar habitat). Simulating conditions during a Mars mission on the ISS will afford higher fidelity for assessing multiple integrated hazards of human spaceflight, however, ground analogs of Mars missions can be used to ensure effective measures and experimental design before testing begins on the ISS. The strategic concepts refined as part of these workshops were brought to a multilateral forum, Mulitlateral Human Research Planel for Exploration (MHRPE), where ISS partner agencies are now discussing implementation plans to provide new opportunities to use the ISS to prepare for deep space exploration over the coming decade. In this publication we present a summary of the international strategic plans for future research that will enable operations, software, and countermeasures to be developed that will reduce the risk to humans during future crewed missions to Mars.