Multiple myeloma is the second most common blood cancer. It is caused by neoplastic expansion of plasma cells that accumulate in the bone marrow, leading to disrupted haematopoiesis and debilitating bone destructions. Prior studies have demonstrated that myeloma cells induce stromal inflammation and immunosuppression via perturbing innate immunity. However, this dogma has primarily derived from in vitro cell assays, in silico modelling and RNA sequencing of dissociated tissues that fail to provide unbiased mechanistic insights and spatial context of cellular interactions. Here, we describe the generation of first-of-its-kind spatially resolved transcriptomic atlas of the murine and human bone marrow at single cell resolution using three independent platforms. Our data suggests a paradigm-shifting theory that myeloma clones alter their local microenvironment in a clone-specific manner, which in turn could influence clonal selection, resistance to therapy and disease relapse.