Despite promising results with immune checkpoint blockade (ICB) therapy, outcomes for patients with brain metastasis (BrM) remain poor. Identifying resistance determinants has been hindered by limited access to patient samples and relevant preclinical models. Here, we developed two mouse melanoma BrM models that reflect the disparate responses to ICB observed in patients. We demonstrate that these models recapitulate the cellular and molecular features of human disease and identify key factors contributing to ICB response. Responsive tumor cells (BR1) expressed inflammatory programs that polarized microglia toward reactive states, characterized by upregulation of MHC-I/-II and immunostimulatory molecules, eliciting robust T cell recruitment. Conversely, resistant melanoma cells (BR3) maintained microglia homeostasis, resulting in poor T cell infiltration. BR1 and BR3 expression signatures correlated positively or negatively with T cell infiltration and BrM patient outcomes, respectively. Our study addresses an unmet need by providing clinically relevant models and uncovering mechanistic insights into BrM ICB responses, identifying potential biomarkers and therapeutic targets.