In recent decades, the regeneration of industrial heritage spaces has become one of the main challenges in the fields of conservation and architectural design, due to shifts in production structures and the decline of original functions. In this context, adaptive reuse has emerged as a common strategy for sustaining these buildings; however, practical experiences indicate that change of use and physical restoration alone cannot guarantee users’ presence and social interactions in these spaces. The present study aims to investigate the role of infill intervention in enhancing the spatial quality of adaptive reuse projects of industrial heritage, and seeks to answer the question of through which physical and spatial mechanisms infill intervention can establish a dynamic relationship between the historical structure and contemporary spatial needs. Adopting a qualitative-analytical approach and employing library research, this study first extracts theoretical components related to spatial quality and vitality, and then, through comparative analysis, examines six notable case studies (four international and two domestic projects) based on five components: spatial organization, quality of movement, relationship between old and new, intermediate spaces, and spatial vitality. The findings indicate that infill intervention contributes to the regeneration of spatial quality through five main mechanisms: preserving and highlighting the historical structure, reorganizing movement relationships, creating transitional spaces, diversifying spatial-temporal experiences, and enhancing permeability and social interactions. Furthermore, the comparison of cases reveals that international projects place greater emphasis on perceptual experience and the creation of distinctive volumetric elements, whereas in domestic projects—due to investment constraints and differences in the nature of use—strategies based on reorganizing movement and strengthening open collective spaces appear to be more effective. Ultimately, by presenting an analytical framework that explains the connection among the three layers of historical structure, infill strategies, and spatial quality, the study emphasizes the necessity of establishing a dynamic balance between preserving historical legibility and responding to contemporary spatial needs, and recommends that in domestic projects, priority be given to movement networks, semi-open spaces, and courtyards as vital infrastructures for spatial vitality.