This chapter presents developments as part of the International Union of Physiological Sciences (IUPS) Physiome Project. Models are multiscale, multispatial and multiphysics, hence, suitable numerical tools and platforms have been developed to address these challenges for the musculoskeletal system. Firstly, we present modelling ontologies including several markup languages used to facilitate storage, sharing and exchange of numerical models. Secondly, custom software tools, CMISS and CMGUI, are then presented in the development of anatomically based geometrical models. Customisation methods are also presented to morph generic models into subject-specific representations. Thirdly, population based modelling and statistical shape analysis methods are presented as efficient techniques that harness the power of big data and imaging databases. These allow prediction of human anatomy from minimal geometric information. Fourthly, a specific example of our framework is presented in the context of a validated orthopaedic clinical tool used for assessing osteolytic defects around implants. Finally, EMG-informed muscle modelling is presented combined with medical imaging to better understand musculoskeletal injury. The problem of NaF PET CT is used to highlight the problem of patellofemoral pain.