Antibody Fc gamma receptors (FcgRs) are present on a wide variety of effector cell populations, including NK cells, dendritic cells (DC), neutrophils, and macrophages. We have previously engineered the Fc domains of antibodies to enhance their affinity for FcgRIIIa, leading to dramatic enhancements in ADCC. While NK cell-mediated lysis occurs predominantly through a single activating receptor FcgRIIIa, activation of antigen presenting cells such as DC and macrophages can also be influenced by the activating receptor FcgRIIa and inhibitory receptor FcgRIIb. In an effort to optimally tune antibodies for effector function, we have engineered a panel of Fc variants with a variety of unique FcgR affinities and specificities, including selective engagement of FcgRIIIa and FcgRIIa over FcgRIIb. Results indicate that whereas NK cell-mediated killing is correlated strongly with FcgRIIIa affinity, phagocytosis by macrophages is dependent on binding to both FcgRIIa and FcgRIIIa. Surprisingly, our data show that absolute FcgRIIb affinity does not negatively impact phagocytosis. Overall these variants have the potential to improve anti-cancer therapy by increasing not only innate effector functions, but also by enhancing adaptive anti-tumor responses, a novel feature of engineered therapeutic antibodies.