Lattice structures based on mechanical metamaterials ‘’exhibit outstanding strength-to-weight ratios and energy absorption capacity, making them ideal for lightweight, load-bearing applications. This study presents a defect-aware, microstructure-guided optimization framework for Ti6Al4V octahedral lattices fabricated via laser powder bed fusion (LPBF). A defect-informed SEA model was proposed, integrating Micro-CT-derived porosity and strut deviation data to refine theoretical predictions, showing strong agreement with experiments. Similarly, by systematically varying unit cell size and strut thickness within a stretch-dominated topology, mechanical strength and energy absorption were significantly improved. Experimental characterization, including uniaxial compression, high-resolution Micro-CT, and SEM analysis, revealed the impact of geometric defects on structural performance. Optimized designs achieved a 43% increase in specific energy absorption and a 40% improvement in peak compressive strength over conventional counterparts. Two-way ANOVA confirmed the statistical significance of geometric parameters and their interaction (p < 0.0001). This work highlights the synergy between topology-driven design and multiscale defect quantification to enable robust, energy-efficient lattice structures for advanced aerospace, biomedical, and crashworthiness applications.