Solid deposition during production, transport, and storage of crude oils leads to significant technical problems and economic losses for the oil and gas industry. The thermodynamic equilibrium between high-molecular-weight components of crude oil, such as asphaltenes, resins, and waxes, is an important parameter for the stability of crude oil. Once the equilibrium is disturbed due to variations in temperature, pressure, and oil composition during production, the solubility of high-molecular-weight waxes decreases. This results in a decrease in the wax appearance temperature (WAT) and the deposit of wax onto solid surfaces. On the other hand, under these conditions, asphaltenes do not interact sufficiently with the resins/waxes and tend to flocculate among themselves and form asphaltene nanoaggregates. The role of waxes during the asphaltene aggregation and deposition has not been appropriately explained yet. The objective of this research study is to describe the interaction of asphaltenes and waxes and subsequently address the specific example of an asphaltenic oil commingled with a wax inhibitor-containing oil during the combination of different oil streams. It is a crucial building block for the development of a suitable and cost-effective strategy for the handling of wax/asphaltene associated flow assurance problems. In this work, the quartz crystal microbalance (QCM) technique has been used for the first time to investigate the effect of waxes and related chemicals, which are used to mitigate wax deposition, on asphaltene aggregation and deposition phenomena. Asphaltene onset point and asphaltene deposition rate have been monitored using QCM at high pressure–high temperature (HPHT) conditions. This study confirms that the different wax inhibitor chemistries result in significant differences in the pour point decrease and viscosity profiles in crude oil. Different wax inhibitors also showed different outcomes regarding the asphaltene deposition tendency. A comprehensive modeling study has also been conducted for mechanistic investigation of experimental results. In this regard, the perturbed chain statistical associating fluid theory equation of state (PC-SAFT EoS) was utilized to model the systems.