The hallmarks of cancer were proposed as a collection of functional features that the cells must acquire during their transformation from normalcy to malignant tumors. However, the cross-talk between tumorigenic cells and the components of the surrounding microenvironment also plays a role in the solid tumors' initiation, progression, and their response to anti-cancer treatments. Here, I will discuss mathematical and computational approaches in modeling of cellular and non-cellular stromal components, their interactions with tumor cells, and their dynamical changes during tumor development and therapies. This will be presented in the context of the micropharmacology modeling framework that we have created. In particular, I will present applications to the extracellular matrix-mediated cell invasion, tumor metabolic landscape-dependent immune cell infiltration, and dynamical changes in metabolic gradients modulating tumor response to hypoxia-activated pro-drugs. These applications will be linked to the classical and updated cancer hallmarks.