Understanding the mechanisms underlying earthquake-induced landslides and assessing seismic responses are crucial for effective mitigation strategies. Earthquakes typically involve a mainshock followed by aftershocks, posing challenges to structures weakened by the mainshock. Highway slope structures, especially those in unsaturated soft-soil slopes, are vulnerable to aftershocks, amplifying the damage caused by the mainshock-aftershock (MSAS) sequence. While existing re- search primarily focuses on the effects of mainshocks on certain structures, there is a notable gap regarding the damage sustained by unsaturated slope structures under MSAS conditions. Address- ing this gap is vital for comprehensive risk assessment and mitigation. To address these challenges, we propose a stochastic model updating approach for seismic reliability analysis. This approach integrates subset simulation with adaptive Bayesian updating and dimensionality reduction using the Karhunen-Lòeve expansion. Shaking table tests on a slope structure with unsaturated red clay soil are conducted to investigate the effects of matrix suction on performance degradation and fail- ure mechanisms. The results reveal spatial variability in soil property parameters, underscoring the need to incorporate this variability into inverse analyses. Traditional deterministic methods or probability-based approaches may overlook such variability. Also, the results indicated our proposed approach enables effective prediction of seismic responses for unsaturated slopes sub- jected to MSAS sequences. By considering spatial variability and the effects of matrix suction, our method offers a comprehensive framework for seismic reliability analysis of unsaturated slope structures.