Given the huge potential of thin film composite (TFC) nanofiltration (NF) membranes for desalination and micro-pollutant removal, two different sets of six NF membranes were synthesized. The molecular structure of the polyamide active layer was tuned by using two different cross-linkers, terephthaloyl chloride (TPC) and trimesoyl chloride (TMC), reacted with tetra-amine solution containing β-Cyclodextrin (BCD). To further tune the structure of the active layers, the time duration of interfacial polymerization (IP) was varied from 1 to 3 min. The membranes were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle (WCA), attenuated total reflectance Fourier transform infra-red (ATR-FTIR) spectroscopy, elemental mapping and energy dispersive (EDX) analysis. The six fabricated membranes were tested for their ability to reject divalent and monovalent ions followed by rejection of micro-pollutants (pharmaceuticals). Consequently, terephthaloyl chloride turned out to be the most effective crosslinker for the fabrication of membrane active layer with tetra-amine in the presence of β-Cyclodextrin using interfacial polymerization reaction for 1 min. The membrane fabricated using TPC crosslinker (BCD-TA-TPC@PSf) showed higher % rejection for divalent ions (Na2SO4= 93%; MgSO4= 92%; MgCl2= 91%; CaCl2= 84%) and micro-pollutants (Caffeine = 88%; Sulfamethoxazole = 90%; Amitriptyline HCl = 92%; Loperamide HCl = 94%) compared to the membrane fabricated using TMC crosslinker (BCD-TA-TMC@PSf). For the BCD-TA-TPC@PSf membrane, the flux was increased from 8 LMH (L/m2.h) to 36 LMH as the transmembrane pressure was increased from 5 bar to 25 bar.