Soft suction cups have been proposed for many applications, including manipulating soft tissues and measuring mechanical properties of the skin. Models that can predict the attachment behavior of such suction cups on their target substrates can help to enable efficient and systematic design. In this work, we develop a finite element model that correctly predicts the attachment behavior of positive-pressure actuated suction cups on both soft and rigid substrates. The model is used in an optimization study to determine a suction cup design that maximizes the attachment force. We propose to use positive-pressure actuated suction cups for anchoring and stabilizing flexible surgical tools during minimally invasive surgery. The optimized suction cup’s ability to resist external forces on rigid and soft substrates and on live porcine tissues is evaluated. It is found that the suction cup could resist up to 3.34 N of normal force and up to 1.59 N of shear force on certain porcine tissues, demonstrating its potential as an anchoring unit for surgical applications.