Cytokine-induced memory-like (CIML) NK cells generated after a brief activation with IL12, IL18 and IL15 exhibit enhanced anti-tumor responses, were safe and associated with promising activity in recent clinical trials. Currently, feeder cells remain the most used method for expanding NK/CAR NK cells. However potential risk of contamination and feeder cell carryover remain as major challenges. Here, we engineered a biodegradable nanomaterial, mesoporous silica rods (MSR), to promote memory-like differentiation, activation, robust proliferation, and efficient transduction of NK cells. To allow induction of CIML NK cell differentiation, IL12 and IL18 were loaded into the MSR pores (C-MSR) where the PK analysis revealed NK cell exposure to IL12 for 48 hours and to IL18 for 72 hours. CIML NK cells generated using C-MSR vs conventional media-based activation revealed similar levels of increased IFNγ responses upon co-culture with K562 cells. The transcriptomic profiles of C-MSR exposed vs conventional CIML NK cells were also similar. Next, to also induce proliferation, IL21 and 4-1BBL were incorporated on the MSR surface via a lipid bilayer (EC-MSR). NK cells cultured with EC-MSR demonstrated ~ 3000-fold expansion in 24 days vs ~ 100-fold seen in the control conditions and showed IFNγ and cytotoxicity responses to K562 cells that were similar to the traditional CIML NK cells. Lastly, EC-MSR scaffold supplemented with Baboon Lentiviral (BaLV) particles at low MOI of 1 demonstrated high transduction (50-70%) which can be attributed to the increased local concentration of virus, enhanced cell-virus contact, and ASCT1/2 expression. We are currently performing in vivo efficacy of the CD19-CAR CIML NK cells developed using EC-MSR. In summary, we have successfully developed a novel biodegradable MSR scaffold that allows CIML induction, expansion, and transduction of NK cells, which should significantly facilitate the development of clinical-grade CAR NK cell products in the near future.