In this research, preparation of waste-derived nanoporous carbon from Iranian asphaltene (IANC), which was further tuned and engineered to exceptionally adsorb amoxicillin (AMX) and metronidazole (MNZ) antibiotics, is reported. Structural tuning and surface modification of IANCs were carried out via melamine treatment and vapor functionalization (i.e., –COOH and –NH₂), respectively. The M-IANC-3 as a superior melamine-modified adsorbent exhibited 43.8% higher mesoporosity compared with that of the pristine one (i.e., P-IANC-3), offering the maximum surface area (2693 m²/g), total pore volume (1.72 cm³/g) and mesopore volume (1.61 cm³/g), which correlated well with its high adsorption capacity of AMX (623 mg/g) and MNZ (447.8 mg/g). Furthermore, the amine functionalized IANC sample (i.e., IANC-NH₂) impressively exhibited ultra-high AMX and MNZ adsorption capacity of 860.6 and 536.5 mg/g, respectively, through hydrogen bonding. Density functional theory calculations also confirmed that the functionalization of IANC with –NH₂ group can greatly enhance the adsorption energy of AMX and MNZ due to more favorable electrostatic and charge-transfer effects. Overall, the results confirmed that the proposed process to optimize and tune the final properties of the adsorbent by melamine modification or amine functionalizing can be efficiently employed to develop high-performance nanoporous structures for antibiotic removal from wastewater effluents.