This manuscript aims to study the effects of drilling factors on the thermal-mechanical properties and delamination experimentally during the drilling of glass fiber reinforced polymer (GFRP). Drilling studies were carried out using a CNC machine under dry cutting conditions by 6 mm diameter with different point angles of ∅ = 100°, 118°, and 140°. The drill spindle speed (400, 800, 1600 rpm), feed (0.025, 0.05, 0.1, 0.2 mm/r), and sample thickness (2.6, 5.3, and 7.7 mm) are considered in the analysis. Heat affected zone (HAZ) generated by drilling was measured using a thermal infrared camera and two K-thermocouples installed in the internal coolant holes of the drill. Therefore, two setups were used; the first is with a rotating drill and fixed specimen holder, and the second is with a rotating holder and fixed drill bit. To measure thrust force/torque through drilling, the Kistler dynamometer model 9272 was utilized. Pull-in and push-out delamination were evaluated based on the image analyzed by an AutoCAD technique. The regression models and multivariable regression analysis were developed to find relations between the drilling factors and responses. The results illustrate the significant relations between drilling factors and drilling responses such as thrust force, delamination, and heat affect zone. It was observed that the thrust force is more inspired by feed; however, the speed effect is more trivial and marginal on the thrust force. All machining parameters have a significant effect on the measured temperature, and the largest contribution is of the laminate thickness (33.14%), followed by speed and feed (29.00% and 15.10%, respectively), ended by the lowest contribution of the drill point angle (11.85%).