Myeloid cells pay contribute to tumour progression, acquired resistance and restrict the efficacy of immune checkpoint inhibitors, and this is often coincides with the phenotypic plasticity of tumour associated macrophages. Accordingly, the manipulation of the macrophage endotype has become a subject of major research activity. Our laboratory has recently identified molecular determinants that are likely to regulate the extent by which macrophages exert either anti-tumourigenic phagocytic or pro-tumourigenic features. Excessive activation of one such determinant, the myeloid-specific Src-family kinase SFK Hematopoietic Cell Kinase (HCK) confers enhanced tumour formation of endogenous and xeno-transplanted solid malignancies in mice reconstituted with bone marrow harbouring a constitutively activating mutation in HCK. Conversely, reconstitution with of hosts with bone marrow from HCK-deficient mice reduces trumour burden as thus treatment op wild-type mice with an HCK-specific small molecule inhibitor. At least in gastric cancer models, we also observe that inhibition of interleukin-33 signaling in submucosal mast cells reduces the activity of tumour-associated macrophages and overall tumour burden. This provides functional evidence for actionable molecular entities by which manipulation of the myeloid compartment confers anti-tumour effects.