Safety Engineering is a broad field with significant societal impact. Within this discipline, fire safety engineering plays a critical role, frequently utilizing fire simulations across diverse scenarios and scales—from small laboratory settings to large-scale wildfire modeling. This chapter addresses key challenges in fire spread modeling through selected simulation examples, including pyrolysis, radiative heat transfer, and a burning tree, each illustrating specific challenges that substantially affect the accuracy of fire spread simulations. Additionally, the chapter introduces a potential approach for managing uncertainties in Computational Fluid Dynamics models using Polynomial Chaos Expansion, applied here to a compartment fire scenario. This chapter is not intended as an exhaustive review of the topic; rather, it aims to underscore the need for further research in the field of fire spread modeling.