Selective separation using efficient high-performance nanofiltration membranes has the potential for widespread application in multiple fields, including dye desalination, industrial wastewater treatment, and resource recovery from different feed streams. This study focused on the design of selective and self-cleaning nanofiltration membranes by incorporating iron aminoclay nanoparticles in a piperazine-based polyamide active layer supported on an ultrafiltration PAN substrate. Fe-AC nanoparticles and thin film nanocomposites (TFNC) were characterized for their morphology, surface chemistry, roughness, and surface area. In terms of wettability/hydrophilicity, TFNC membranes with Fe-AC incorporated had the lowest contact angle of 33.5°, while that of the pristine TFNC0 membrane was 60.5°. They also had a higher surface negative zeta potential and smoother surface morphology. The TFNC membranes also exhibited higher water fluxes and enhanced selectivity towards molecular separation compared to the control membranes. The water flux of the optimized AC polyamide membrane, TFNC3, was 19.70 ± 0.5 LMH (L.m−2.h−1), while that of the pristine TFNC0 membrane was 4.85 ± 0.6 LMH at 4 bar. 98.0–99.0 % rejection of model organic moieties was achieved at a constant flux (Congo red, Eriochrome Black T, methylene blue, Rhodamine 6G, and Crystal violet). When simulated wastewater was purified, the Fe-AC TFNC showed 98.0 % rejection of dyes and 20.0 % rejection of inorganic salts. In long-term filtration studies (>210 h) using simulated wastewater spiked with multiple foulants, >98.0 % rejection of organic matter and foulants was recorded with a stable long-term flux profile. A leaching study confirmed that the membranes were structurally stable, even after the self-cleaning process and at elevated temperatures, without any significant reduction in flux or rejection. Comparing the fouling performance between TFNC3 membranes and commercial reverse osmosis (RO) membranes, the FDR and Flux Recovery Ratio (FRR) values of commercial RO membranes were 58.0 % and 73.0 %, while those of TFNC3 were 47.0 % and 97.0 %, respectively. The results show that the membranes have lower fouling values and higher FRR values when iron clay is present. These results demonstrate the potential of the membranes for effective pre-treatment of various industrial wastewaters and selective separation.