Thin-film nanocomposite (TFN) membranes are the third-generation membranes being explored for nanofiltration applications. Incorporating nanofillers in the dense selective polyamide (PA) layer improves the permeability–selectivity trade-off. The mesoporous cellular foam composite Zn-PDA-MCF-5 was used as a hydrophilic filler in this study to prepare TFN membranes. Incorporating the nanomaterial onto the TFN-2 membrane resulted in a decrease in the water contact angle and suppression of the membrane surface roughness. The pure water permeability of 6.40 LMH bar−1at the optimal loading ratio of 0.25 wt.% obtained was higher than the TFN-0 (4.20 LMH bar−1). The optimal TFN-2 demonstrated a high rejection of small-sized organics (>95% rejection for 2,4-dichlorophenol over five cycles) and salts—Na2SO4(≈95%) > MgCl2(≈88%) > NaCl (86%) through size sieving and Donnan exclusion mechanisms. Furthermore, the flux recovery ratio for TFN-2 increased from 78.9 to 94.2% when challenged with a model protein foulant (bovine serum albumin), indicating improved anti-fouling abilities. Overall, these findings provided a concrete step forward in fabricating TFN membranes that are highly suitable for wastewater treatment and desalination applications.