Polymer-coated silica nanoparticles (PSiNPs) have been experimentally investigated in core- and micro-scale studies for enhanced oil recovery (EOR). Wettability and flow rate have a considerable effect on oil displacement in porous media. This work investigates the efficiency of PSiNPs for oil recovery on micro-scale at three wettability states (water-wet, intermediate-wet, and oil-wet). In addition, a cluster mobilization regime is considered in all experiments. A microfluidic approach was utilized to perform flooding experiments with constant experimental settings such as flowrate, pore-structure, initial oil topology, porosity, and permeability. In this study, the wettability of the microfluidic chips was altered to have three states of wettability. Firstly, a micro-scale study (brine-oil-glass system) of each wettability condition effect on flow behavior was conducted via monitoring dynamic changes in the oleic phase. Secondly, the obtained results were used as a basis to understand the changes induced by the PSiNPs while flooding at the same conditions. The experimental data were extracted by means of image processing and analysis at a high spatial and temporal resolution. Low injection rate experiments (corresponding to ~1.26 m/day in reservoir) in a brine-oil-glass system showed that the waterflood invaded with a more stable front with a slower displacement velocity in the water-wet state compared to the other states, which had water channeling through the big pores. As a result, a faster stop of the dynamic changes for the intermediate- and oil-wet state was observed, leading to lower oil recoveries compared to the water-wet state. In a cluster mobilization regime, dynamic changes were noticeable only for the oil-wet condition. For the aforementioned different conditions, PSiNPs improved oil displacement efficiency. The usage of PSiNPs showed a better clusterization efficiency, leading to a higher mobilization, smaller remaining oil clusters, and lower connectivity of the residual oil. The knowledge from this experimental work adds to the understanding of the behavior of polymer-coated silica nanoparticles as a recovery agent at different wettability states and a cluster mobilization regime.