In this work, a mixed lubrication model, applicable to cam-roller contacts, is presented. The model takes into account non-Newtonian, thermal effects, and variable roller angular velocity. Mixed lubrication is analyzed using the load sharing concept, using measured surface roughness. Using the model, a quasi-static analysis for a heavily loaded cam-roller follower contact is carried out. The results show that when the lubrication conditions in the roller-pin contact are satisfactory, i.e., low friction levels, then the nearly “pure rolling” condition at the cam-roller contact is maintained and lubrication performance is also satisfactory. Moreover, non-Newtonian and thermal effects are then negligible. Furthermore, the influence of roller-pin friction coefficient on the overall tribological behavior of the cam-roller contact is investigated. In this part, a parametric study is carried out in which the friction coefficient in the roller-pin contact is varied from values corresponding to full film lubrication to values corresponding to boundary lubrication. Main findings are that at increasing friction levels in the roller-pin contact, there is a sudden increase in the slide-to-roll ratio (SRR) in the cam-roller contact. The value of the roller-pin friction coefficient at which this sudden increase in SRR is noticed depends on the contact force, the non-Newtonian characteristics, and viscosity–pressure dependence. For roller-pin friction coefficient values higher than this critical value, inclusion of non-Newtonian and thermal effects becomes highly important. Furthermore, after this critical level of roller-pin friction, the lubrication regime rapidly shifts from full film to mixed lubrication. Based on the findings in this work, the importance of ensuring adequate lubrication in the roller-pin contact is highlighted as this appears to be the critical contact in the cam-follower unit.