Understanding the mechanisms of interaction at the interface between biomacromolecules and materials is vital for the development of effective immobilization processes. The complex interplay between biological systems and material reactivity poses several challenges in current enzyme immobilization protocols. This includes accurately measuring the activity of adsorbents, overcoming limitations in mass transfer, and assessing the effects of the microenvironment. Additionally, the scarcity of experimental data available for developing and validating enzyme immobilization techniques indicates that this field is still in its early stages. To address this complexity, it is essential to pursue accurate orientation and conformational analysis of structures, alongside predictions regarding the long-term stability of the adsorbent-adsorbate complex. Employing predictive modeling supported by accurate kinetic models that elucidate diffusion and enzyme-support interactions, can not only bridge theoretical gaps but also deepen our understanding of the underlying mechanisms involved. This chapter addresses key protocols and techniques from the multidisciplinary approach which combines material science, protein biochemistry, chemical engineering, and computational modeling. Through addressing these challenges, researchers can advance the development of more efficient immobilization technologies, facilitating a diverse range of applications in biomedical field and significantly enhance healthcare solutions.