Kinome profiles of endometrial tumors and normal tissues have been determined using Multiplexed Inhibitor Beads and Mass Spectrometry. Overexpression of SRPK1 in endometrial tumors was observed, which was associated with poor survival. Inhibition of SRPK1 in endometrial cancer cells revealed SRPK1 was integral for growth under serum-starved conditions. Compensatory activation of EGFR, IGF1R, and AKT promoted resistance to SRPK1 inhibitor SPHINX31. Combination therapies involving SRPK1 and EGFR or IGF1R inhibitors synergized to block growth and survival of endometrial cancer cells.