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A 3-year field experiment was setup to address the threat of underground water depletion and sustainability of agrifood systems. Subsurface drip irrigation (SDI) system combined with nitrogen management under conservation agriculture-based (CA) maize-wheat system (MWS) effects on crop yields, irrigation water productivity (WPi), nitrogen use efficiency (NUE) and profitability. Grain yields of maize, wheat, and MWS in the SDI with 100% recommended N were significantly higher by 15.8%, 5.2% and 11.2%, respectively, than conventional furrow/flood irrigation (CT-FI) system. System irrigation water savings (~ 55%) and the mean WPi were higher in maize, wheat, and MWS under the SDI than CT-FI system. There was saving of 25% of fertilizer N in maize and MWS whereas no saving of N was observed in wheat. Net returns from MWS were significantly higher (USD 265) under SDI with 100% N (with no subsidy) than CT-FI system despite with higher cost of production. The net returns were increased by 47% when considering a subsidy of 80% on laying SDI system. Our results showed a great potential of complementing CA with SDI and N management to maximize productivity, NUE, and WPi, which may be economically beneficial and environmentally sound in MWS in Trans-IGP of South Asia.