The invention provides an in vivo individualized systemic immunotherapeutic method and device. The method includes, in a non-sequential manner: (1) increasing release amount of tumor antigens at a tumor site; (2) at the tumor site, increasing level of proteins capable of adhering to and/or wrapping the tumor antigens; (3) at the tumor site, increasing level of dedicated antigen-presenting cells involved in immunity, and establishing, between the dedicated antigen-presenting cells and immune effector cells, a close connection capable of activating the immune effector cells; and (4) at the tumor site, increasing level and improving function of the immune effector cells. The steps (1)-(4) each reaches a maximum value at a respective time which overlaps with each other maximally, as well as at a respective site which overlaps with each other maximally. The invention combines oncolytic therapy and immunotherapy, in individualized systemic immunotherapy, and provides significantly improved therapeutic effect.