The Kirsten Rat Sarcoma Virus (KRAS) oncoprotein, one of the most prevalent mutations in cancer, has been deemed undruggable for decades. The hypothesis of this work was that delivering anti-KRAS monoclonal antibody (mAb) at the intracellular level could effectively target the KRAS oncoprotein. To reach this goal, we designed and developed tLyP1-targeted palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs) adapted for the association of bevacizumab as a model mAb. Selected candidates with adequate physicochemical properties (below 150 nm, neutral surface charge), and high drug loading capacity (>10%, w/w) were adapted to entrap the antiKRASG12V mAb. The resulting antiKRASG12V-loaded HANAs exhibited a bilayer composed of HAC16 polymer and phosphatidylcholine (PC) enclosing a hydrophilic core, as evidenced by cryogenic-transmission electron microscopy (cryo-TEM) and X-ray photoelectron spectroscopy (XPS). Selected prototypes were found to efficiently engage the target KRASG12V and, inhibit proliferation and colony formation in KRASG12V-mutated lung cancer cell lines. In vivo, a selected formulation exhibited a tumor growth reduction in a pancreatic tumor-bearing mouse model. In brief, this study offers evidence of the potential to use nanotechnology for developing anti-KRAS precision therapy and provides a rational framework for advancing mAb intracellular delivery against intracellular targets.