Charles Bridge in Prague is one of the most famous monuments of the European architectural heritage. As typical of complex historical structures, a realistic quantitative computational assessment of the bridge response should address multi-physics, multi-scale, time-dependent and three-dimensional aspects of the problem. In this paper, an example of such a study is reported. To keep the model complexity manageable, the analysis is executed in a fully-uncoupled format, where the outputs of individual simplified sub-problems concerning mainly transport phenomena serve as inputs for the dominant part: detailed non-linear three-dimensional and mechanicsoriented simulations of selected bridge segments. The obtained results not only provide the basis for reconstruction works currently in progress, but also demonstrate the applicability and limitations of multi-scale and multi-physics paradigms when faced with complex practical engineering problems.