Immunotherapy holds great promise to improve the cancer treatment. The uptake of tumor-associated antigens (TAAs) by tumor-infiltrating antigen-presenting cells (e.g., macrophages) is the essential step for achieving efficient antitumor immunity. However, tumor cells usually evade phagocytosis of macrophage, resulting in inefficient TAA uptake. Herein, we demonstrate a bi-specific macrophage nano-engager (BiME) that can enhance the recognition and phagocytosis of tumor cells by macrophages, thereby achieving effective TAA uptake and presentation. BiME is composed of an albumin-based nanoparticle with a surface of crosslinked polymer network containing tumor-targeting moieties, macrophage-targeting moieties, and detachable PEG. Upon entering tumor tissues, BiME detaches the PEG and triggers phagocytosis of tumor cells by macrophages. As a result, BiME converts the tumor cells into an in situ vaccine, thereby activating robust T cell-dependent antitumor responses. By changing the tumor-targeting moieties, BiME may become a universal strategy to enhance the antitumor immunity against a broad range of solid tumors. (c) 2021 Elsevier Ltd. All rights reserved.