Professional phagocytes such as dendritic cells (DCs) clear dead cells to prevent secondary necrosis and to acquire antigens for presentation. Although numerous “eat-me” signals from dying cells have been characterized, whether the metabolic state of a cell prior to death influences its subsequent uptake by DCs remains unclear. To address this, we performed unbiased metabolomic profiling of factors released from apoptosing cells to define a clear signature of the secretome of dying cells. Pharmacological modulation of implicated pathways in target cells prior to cell death induction revealed the secretion of polyamines to be a critical regulator of DC efferocytosis. Inhibition or deletion of Odc1, the rate-limiting enzyme for polyamine synthesis, in pre-apoptotic cells markedly reduced the uptake of dead cells by DCs in vitro and in vivo, indicating that DCs rely on polyamines provided by the dying cells rather than those generated intrinsically. This dependency was specific to DCs, as macrophage phagocytosis was insensitive to the polyamine content of dead cells. Putrescine, but not spermidine or spermine, restored efficient uptake of polyamine-depleted corpses, identifying putrescine as the direct mediator of this process. Employing FRET imaging, we found that DCs interacting with polyamine-deficient corpses exhibited reduced Rac1 activity at the cell–cell interface, implicating impaired actin cytoskeletal remodeling as a mechanistic consequence of polyamine loss. Functionally, uptake of polyamine-deficient dead cells resulted in diminished migration of antigen-loaded DCs to draining lymph nodes. Vaccination with Odc1-deficient, OVA-expressing dead cells led to defective priming of OVA-specific CD8+ T cells and reduced antitumor immunity in the B16-OVA melanoma model. Collectively, these findings identify polyamine availability within dying cells as a previously unrecognized determinant of DC phagocytosis and subsequent adaptive priming, demonstrating that the metabolic state of cells at the time of death can modulate DC-mediated immunity