As is well acknowledged that mechanical properties of material extrusion (ME) additive manufacturing polymers are highly related to processing parameters. Meanwhile, the yield strength is one of the key properties of a material, which critically affects a component’s manufacturing and further application. To reveal the effect of printing parameters such as layer thickness, printing speed and deposition orientation on the yield strength of ME polymers without extensive experimental researches, a novel, integrated prediction model accounting for processing-structure-property relationship is put forward. In this model, processing related representative volume element (RVE) of unidirectional ME polymers is firstly estimated by combining the volume conservation method and thermal-sintering model. Next, assuming raw polymers to be homogenous, isotropic, and ideal elastic-plastic, a multiscale approach integrating Hill model and homogenization theory is presented to acquire the stress-strain curves of anisotropic ME polymers under externally applied loadings. In this procedure, the dependence of RVE’s estimated anisotropic parameters in Hill model on their external loading states is paid attention. By this means, the three-dimensional yield behavior of ME polymers, including the off-axis yield strength, can be obtained. The validity of the proposed method is examined by comparing with existing test data in literature or our measured ones. Finally, explicit discussions are made. Many valuable conclusions are drawn, which may be of unique significance for the future processing optimization and quality improvement of final products.