Purpose: To investigate the optimal combination of factors (finish line, scanning, and ceramic processing) to achieve the best values of both adaptation and fracture load for lithium disilicate crowns (LD). Materials and Methods: Two abutment preparations, chamfer (C) and rounded shoulder (S), were produced with a dentin analog material and scanned with either extraoral (E) or intraoral (I) scanners. Images were processed using CAD software to design a premolar. Blocks of LD were milled using a CAD/CAM system (CAD). For the press technique (PRE), crowns were first 3D printed using a polymeric material, then heat-pressing protocol was performed. Design of experiments was used to plan four experimental groups (n = 10): CAD-CI, CAD-SE, PRE-CE, and PRE-SI. Two dependent variables were analyzed: adaptation, measured using the replica technique; and fracture load of the cemented crowns. Fractographic analysis was performed. Data were analyzed using ANOVA and regression statistical analyses. Results: There was no significant effect of the scanning method and finish line on the gap thickness in the different regions. For the processing method, CAD resulted in larger gap thickness in the occlusal, axial angle, and marginal areas and a smaller gap in the axial area (P < .001). The investigated factors had no effect on the fracture load. Yet, PRE-CE was considered the optimum design because it achieved 100% of the desired fracture load (>1000 N) and 40% adaptation (< 200 µm). Conclusions: The optimum combination of factors for all-ceramic crowns is chamfer abutment preparation, extraoral scanning, and the press technique (combined with 3D printing). Int J Prosthodont 2023;36:e103–e118