Si Pangilinan tinogdas an First Pacific kan 1981 asin nagsirbe bilang Managing Director hanggan 1999. Siya natoka man bilang Executive Chairman sagkod Hunyo, 2003 kun kasoarin naman ginibo na siyang sabay na CEO asin Managing Director. Sa laog kan Pacific Group, kapot niya an katongdan bilang President Commissioner kan  P.T. Indofood Sukses Makmur Tbk, an pinakadakulang kompanya sa kakanon sa Indonesya. Nangaranan siyang Chairman kan Philippine Long Distance Telephone Company (PLDT) pakatapos na magsirbe bilang Presidente asin CEO sagkod Pebrero 2004. Siya nagsirbe man  komo Chairman kan Maynilad Water Services, Inc., Metro Pacific Tollways Corporation, Medical Doctors, Inc., Metro Pacific Investments Corporation, Landco Pacific Corporation, Pilipino Telephone Corporation, Smart Communications, Inc. asin kan  Manila Metro Rail Transit System.