Abstract A virtual test blanket module (VTBM) has been envisioned as a utility to aid in streamlining and optimizing the US ITER TBM design effort by providing an integrated multi-code, multi-physics modeling environment. Within this effort, an integrated simulation approach is being developed for TBM design calculations and performance evaluation. Particularly, integrated thermo-fluid/thermal-stress analysis is important for enabling TBM design and performance calculations. In this paper, procedures involved in transient coupled thermo-fluid/thermal-stress analysis are investigated. The established procedure is applied to study the impact of pulsed operational phenomenon on the thermal-stress response of the TBM first wall. A two-way coupling between the thermal strain and temperature field is also studied, in the context of a change in thermal conductivity of the beryllium pebble bed in a solid breeder blanket TBM due to thermal strain. The temperature field determines the thermal strain in beryllium, which in turn changes the temperature field. Iterative thermo-fluid/thermal strain calculations have been applied to both steady-state and pulsed operation conditions. All calculations have been carried out in three dimensions with representative MCAD models, including all the TBM components in their entirety.