The electrostatic Layer-by-Layer (LbL) assembly process holds promise in customising the surface and bulk properties of bone tissue-engineered scaffolds. This research aimed to create functionalised, mechanically robust multilayer nanocomposite coatings on highly porous 3D templates to enhance in vivo functionality. The nanocomposite LbL-coated scaffolds were fabricated using 1 wt.% solutions of poly-L-lysine (+), polyglutamic acid (-), polydiallydimethylammonium (+), and 0.5 wt.% montmorillonite-nanoclay (-). Optimised coating materials system and process parameters under dynamic LbL-coating conditions were employed. Deposition of the nanocomposite LbL-coating on polyureathane (PU) scaffolds maintained the highly interconnected structure of the PU, resulting in scaffolds with 79 ± 1.1% porosity. This process led to a 260-fold enhancement in mechanical properties, increasing from 0.082 to 21.64 MPa under fully optimised conditions with 100 quadlayers deposited. To enhance mechanical properties under hydration, chemical crosslinking was applied to the optimised LbL-coated scaffolds using a 1 wt.% aqueous tannic acid (TA) solution. The 1 wt.% TA crosslinking exhibited optimal behaviour, with hydrated TA crosslinked scaffolds retaining 75% of their mechanical performance post-hydration. SEM analysis confirmed that a uniform and robust multilayer nanocomposite coating was achieved using LbL process. Surface hydrophilicity analysis showed a decrease in the contact angle from 138.8 ± 2.85° for uncoated to 70.28 ± 3.10° for crosslinked scaffolds. In vitro studies where, the scaffolds seeded with pre-osteoblast cells (MC3T3-E1) showed minimal evidence of cytotoxicity, with cell viability > 100% in crosslinked scaffold extracts after 48 h and 97.31% ± 2.17% cell attachment to the scaffold after 24. Increased cell metabolic activity was observed over 14 days, indicating proliferation. SEM imaging confirmed uniform cell layers with cell filopodia interacting with the scaffold pore surface on Days 7 and 14. The multifunctional crosslinked LbL-coated scaffolds demonstrated in this study represent a promising approach for enhancing the physiomechanical properties of open-cell structures with an initial positive impact on pre-osteoblast cellular responses for bone tissue engineering applications.