Microencapsulation by spray-drying is a process used in the stabilization of active compounds from various natural sources, such as tomato by-products, with the purpose to be used as additives in the food industry. The aim of this work was to study the effects of wall material and spray drying conditions on physicochemical properties of microcapsules loaded with lycopene rich extract from tomato pomace. The assays were carried out with ethanolic tomato pomace extract as core material and arabic gum or inulin as wall materials. A central composite rotatable design was used to evaluate the effect of drying air inlet temperature (110–200 °C) and concentration of arabic gum (5–35 wt %) or inulin (5–25 wt %) on the antioxidant activity, encapsulation efficiency, loading capacity, and drying yield. SEM images showed that the produced particles were in the category of skin-forming structures. The most suitable conditions, within the ranges studied, to obtain lycopene loaded microparticles were a biopolymer concentration of 10 wt % for both materials and an inlet temperature of 200 and 160 °C for arabic gum and inulin, respectively. Arabic gum and inulin possessed a good performance in the encapsulation of tomato pomace extract by spray drying. It is envisaged that the capsules produced have good potential to be incorporated in foods systems with diverse chemical and physical properties.