Damage in the bonding interface is a significant factor that leads to premature failure of dental bonded restorations. The imperfectly bonded dentin-adhesive interface is susceptible to hydrolytic degradation and bacterial and enzyme attack, severely jeopardizing restorations’ longevity. Developing caries around previously made restorations, also called “recurrent or secondary caries,” is a significant health problem. The replacement of restorations is the most prevailing treatment in dental clinics, leading to the so-called “tooth death spiral”. In other words, every time a restoration is replaced, more tooth tissue is removed, increasing the size of the restorations until the tooth is eventually lost. This process leads to high financial costs and detriment to patients’ quality of life. Since the complexity of the oral cavity makes prevention a challenging task, novel strategies in Dental Materials and Operative fields are required. This article briefly overviews the physiological dentin substrate, features of dentin bonding, challenges and clinical relevance. We discussed the anatomy of the dental bonding interface, aspects of the degradation at the resin-dentin interface, extrinsic and intrinsic factors affecting dental bonding longevity, perspectives on resin and collagen degradation and how these subjects are connected. In this narrative review, we also outlined the recent progress in overcoming dental bonding challenges through bioinspiration, nanotechnology and advanced techniques to reduce degradation and improve dental bonding longevity.