Selective laser trabeculoplasty (SLT) emerges as a first-line treatment for newly diagnosed open-angle glaucoma and ocular hypertension. However, the interindividual response to SLT considerably varied. Large-scale clinical investigations concerning predictive factors for SLT effectiveness are limited. This study aimed to identify baseline predictors of the percentage intraocular pressure (IOP)-lowering effectiveness of SLT using an alternative mathematical approach. Mathematical equations of IOP under the steady state of aqueous humour flow were formulated. The conclusive equation integrates physiological variables, including trabecular outflow facility, uveoscleral outflow fraction, plasma protein concentration, albumin/globulin ratio, mean arterial pressure, episcleral venous pressure, and plasma osmolarity. The equation was employed to estimate the percentage of IOP reduction following SLT and subsequently subjected to global sensitivity analysis to determine significant predictors of the IOP-lowering effect of SLT using the Monte Carlo simulation of 8,192 samples. In the current model, a 50% improvement in the trabecular outflow facility impacted by SLT is associated with a mean percentage IOP reduction of 16.6%. Lower baseline trabecular outflow facilities were the strongest predictors, showing a correlation with greater effectiveness of SLT in terms of percentage of IOP reduction. The second most influential factor includes baseline uveoscleral outflow fraction, followed by baseline episcleral venous pressure. Specifically, lower baseline uveoscleral outflow fraction and episcleral venous pressure were found to be correlated with increased effectiveness of SLT. Baseline levels of plasma protein concentration, albumin/globulin ratio, mean arterial pressure, and plasma osmolarity have minimal impact on SLT success or failure. This study identifies baseline trabecular outflow facilities as the strongest predictor of SLT effectiveness. The results suggested that pre-SLT medical treatment that augments uveoscleral outflow and/or trabecular outflow facilities could compromise the effectiveness of subsequent SLT in terms of percentage IOP reduction compared to those who never received pre-SLT medication.