Bacterial implant-related infections have been pointed out as the leading cause of metal implant failure. Recently, nanotexturization of biomaterials surface associated with antibiotic loading revealed itself as a promising strategy for enhancing osseointegration while mitigating bacterial infections. However, fewer studies describe the effects of multi-step local drug delivery. This study investigates 1 mg Cefazolin Sodium (CS) release from anodic nanotextured titanium-based devices and the effect of polymer coverage with differential aqua solubility characteristics (Chitosan—CH and Carboxymethylcellulose—CM). Results show that larger inner pore diameters are related to longer drug release times on uncovered samples. The polymeric coverage decreases the release rates, highlighting the Carboxymethylcellulose boosting the Cefazolin release time by 51–77 fold. All biomaterials exhibited a low or absent hemolytic activity and considerable bacteria inactivation. In summary, 40 °C/CM-based samples present the most promising results for drug release devices.