Developing sustainable structural materials from agricultural and industrial bio-waste remains critical for mitigating environmental impacts and replacing non-biodegradable synthetic reinforcements. Unreinforced epoxy resins exhibit inherent brittleness and low impact resistance, whereas un-optimized bio-filler additions frequently induce particulate agglomeration and weak interfacial bonding. In this study, EPOCHEM epoxy resin was hybridized with eco-friendly particulates derived from Anambra cow bones and Mangifera indica (mango) seed shells. The bio-wastes were synthesized through controlled carburization, hydrothermal treatment, and calcination processes to yield fine particulate ash. Hybrid composites were fabricated using a hand lay-up technique with a standard resin-to-hardener ratio. Response Surface Methodology (RSM) based on a Central Composite Design (CCD) was employed to optimize the chemical treatment parameters—specifically sodium hydroxide (NaOH) concentration and soaking duration—to maximize the ultimate tensile strength of the bio-waste hybrid composites. Mechanical testing (tensile and hardness), thermal stability, dry sliding wear, FTIR functional group analysis, and SEM-EDS microstructural characterization were conducted. Analysis of Variance (ANOVA) confirmed high statistical model significance () with a non-significant lack of fit (). Optimal processing conditions were established at 6.5 wt.% NaOH concentration and a 4.2-hour soaking duration, yielding a peak experimental tensile strength of 68.45 MPa with a desirability score of 0.985. The SEM microstructural evaluation verified a homogeneous particulate dispersion and improved interfacial adhesion, preventing early matrix cracking. Overall, the hybridization of Mangifera indica shell ash and cow bone ash provides a cost-effective, environmentally friendly reinforcement strategy that significantly enhances the mechanical and microstructural performance of epoxy composites for lightweight semi-structural automotive and industrial paneling applications.