Here, titanium porous substrates were fabricated by a space holder technique. The relationship between microstructural characteristics (pore equivalent diameter, mean free-path between pores, roughness and contact surface), mechanical properties (Young’s modulus, yield strength and dynamic micro-hardness) and bacterial behavior are discussed. The bacterial strains evaluated are often found on dental implants: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The colony-forming units increased with the size of the spacer for both types of studied strains. An antibiofouling synthetic coating based on a sulfonated polyetheretherketone polymer revealed an effective chemical surface modification for inhibiting MRSA adhesion and growth. These findings collectively suggest that porous titanium implants designed with a pore size of 100–200 µm can be considered most suitable, assuring the best biomechanical and bifunctional anti-bacterial properties.