Natural Killer (NK) cells represent a cornerstone of innate immunity with immense potential for "off-the-shelf" cancer immunotherapy. However, sub-optimal differentiation and imprecise cell-fate specification remain significant bottlenecks in translating stem cell-derived therapies. we investigated the influence of donor cell types on the epigenome and differentiation potential of human induced pluripotent stem cells (iPSCs). By comparing sources including Cord Blood CD34+, PBMCs, and fibroblasts, we identified that CD34+ HSPC-derived iPSCs yield the highest expansion potential and superior cytotoxicity against tumor targets. Utilizing single-cell RNA sequencing and lineage tracing, we mapped the developmental trajectories of three distinct in-vitro populations—conventional CD7+, CD7-, and myeloid NK cells, revealing that maintaining a CD56bright phenotype is critical for successful expansion. Furthermore, our in-silico perturbation models successfully predicted and validated that modulating epigenetic regulators like EZH2 can significantly enhance NK cell purity and functional potency. These findings establish a robust platform for engineering high-quality, scalable PSC-NK cells