Mg-Zn-Ca alloy is a promising candidate for orthopaedic implants such as bone plates and screws, as it has a similar mechanical strength and elastic modulus to bone, and it degrades in the body without causing toxicity or inflammation. Drilling studies are necessary to optimize the drilling process parameters, to evaluate the machinability and surface integrity of Mg-Zn-Ca alloy, and to ensure the effective and efficient drilling for various applications in the medical and engineering fields. The present experimental study emphasizes the influence of Ca content, biofriendly coolants and their combined effect with standard drill bits on the surface quality and axial thrust force in the drilling operation of Mg-Zn-Ca alloy. The drilling parameters such as cutting speed, feed rate, standard tools, bio-compatible coolants were optimized with respect to the amount of Ca in the Mg-Zn alloy. The axial thrust force and average surface roughness of drilled holes were considered as response of the experiments. The drilled surfaces were measured for average surface roughness in the transverse direction along the centre path of the drilled hole and a qualitative analysis was also carried out using advanced confocal microscope. The results revealed that the cutting speed among continuous factors significantly influenced the axial thrust force and average surface roughness. The effect of categorical factors was assessed using a regression based ranking method. The results of statistical analysis revealed that high speed steel, and vegetable oil offered improved surface quality, whereas the coconut oil showed low axial thrust force. The liquid nitrogen showed high value of axial thrust force and average surface roughness due to the brittleness induced by cryogenic coolant before drilling operation.