Cancer drugs that target key mutations often follow a pattern of initial significant response, followed by relapse, indicating the emergence of resistance to the treatment. The evolutionary nature or cancer can explain this response where from within the heterogeneous population of tumour cells driving the tumour there is a population of cells that evolve resistance to the treatment drugs. In addition to this mechanism, the environment in which the tumour lives is known to modulate drug resistance, so called microenvironment-mediated drug resistance (EMDR). In this talk I will describe a mathematical framework that can capture the interactions between the tumour and the microenvironment in the presence of treatment drugs, across experimental, spatial, and temporal scales. With our model we investigate in silico how processes operating at different spatial and temporal scales result in a local environment that enables survival and resistance observed clinically and experimentally. Preliminary results hint at the emergence of transient protective niches which facilitate EMDR, resulting in localised residual disease, and offer insight into therapeutic strategies that can successfully control the emergence of drug resistance.