Lytic granule (LG) positioning is inherent to disease protection as it allows for concentration of the lytic machinery towards a single (often malignant or infected) cell, while sparing the surrounding healthy tissue. This is in part mediated by the process of LG convergence, where these specialized organelles concentrate around the MTOC and Golgi apparatus and subsequently are trafficked to the Immune synapse (IS). Convergence is mediated by the mobilization and transient interactions of LG with microtubules and Golgi. Previously, we demonstrated that blocking convergence via chemical and genetic approaches during NK cell activation results in stochastic LG dispersal in the cytoplasm. These dispersed LG are consequently released outside the context of the IS and induce bystander killing. We recently reported a human NK cell deficiency resulting from dispersed LG impairing antiviral defense. More diffused killing, however, can likely be advantageous for therapeutic purposes when using cytotoxic cells to treat solid tumors. Promoting multi-directional degranulation in a heterogeneous and immune-suppressive tumor microenvironment unleashes maximal anti-tumor cytotoxicity; fully utilizing each degranulation event and increasing cytotoxic killing capacity of a heterogeneous tumor through enhanced collateral damage. Here we demonstrate multiple strategies where combining plasma membrane anchoring motifs to LG-associating proteins enables active redirection of the LG to the cell cortex. Deliberate repositioning and targeting of LG to the cell membrane in activated NK cells increases degranulation after triggering and promotes non-directional bystander killing in in vitro models and 3D tumor models. Harnessing and controlling LG positing to the membrane could be a cross-platform implementable strategy, independent of tumor antigen targeting approach to facilitate solid tumor cancer immunotherapy.