This research aims to study the relationship between the physical structure and the functional occupation of a downtown Istanbul district Tarlaba, which throughout the last century has faced tremendous changes leading heterogeneity in social structure along with lower levels of environmental quality. As many migrants primarily preferred to settle in the district considering the economic conditions and proximity to urban amenities, the socio-cultural background such as the traditional life styles and customs of the new comers usually contradict with the physical possibilities of the built environment. The district has gone through changes from housing a homogenous bourgeoisie population, to heterogeneous ghetto groups. Recent studies on the area, cover the interrelation of socio-demographic change, physical deterioration and especially outcomes of crime factor in Tarlaba. These studies expose certain relationships between parameters such as change of users, gentrification process, functional use of buildings, and eventually change of quality in the residential environment. This research aims to expose effects of physical, social and functional setting preferences, to environmental quality, regarding the changes manipulated by the main arteries, topographic and the syntactic structure of the main arteries bordering the district and the selected vertically connecting streets. The upper artery of the case study area, Tarlaba.Boulevard is the core of the mentioned socio-cultural change. The boulevard maintains its unique position connecting the old, thus administrative city centre to the modern, thus cultural city centre Taksim, while comprising a slowly spreading commercial strip among residential units. The lower artery of the case study area, Dolapdere Street, on the other hand, carries one of the most heavy traffic loads of vehicle transportation, with connections to main highways. Owing to its frequented location, and relatively larger building plots, Dolapdere Street has been housing many small factories and manufacturers, while decreasing the proportion of residential population. The vertical streets connecting these two arteries also expose the effects of socio-cultural change to the changes in land uses. The research is composed of a three-staged case study where the first stage exposes the functional occupancy of the selected arteries, the second phase covers interviews with the selected floor occupants, and the third stage analyses the topographic character input of the area through syntactic structure of the streets. The comparative analyses of the data will show the implications on the relationship between environmental qualities through functional occupancy preferences of the plots. The results of the research is considered to expose the relations between the character and dispersion of non-residential functions, the effects of these functional occupancies to the criminal vulnerability of the neighbourhood environment and the syntactic structure of the streets.