The intricate composition of pyrolysis bio-oil necessitates the development of reliable phase equilibrium models, with a specific focus on liquid−vapor equilibrium pertinent to both condensation design and distillation, especially when utilizing nonwood feedstocks. Four key challenges intrinsic to pyrolysis bio-oil are scrutinized: the selection of an appropriate phase equilibrium model, formulation of a suitable surrogate mixture, representation of the elusive high-molecular-weight residue fraction, and the estimation of absent thermophysical properties. Despite a discernible inclination toward activity coefficient models, the literature reveals a diverse array of phase equilibrium models, pointing to the indispensability of considering a nonideal liquid phase and raising concerns about the reliability of certain models in the absence of comprehensive experimental data. The judicious choice of a surrogate mixture emerges as pivotal, given the prevalence of unknown components and the dearth of precise compound-specific data, foreseeing a future where diverse surrogate mixtures coexist. Existing surrogate mixtures are reviewed and recommendations given to guide effective design of such mixtures. The absence of thermophysical properties for pyrolysis bio-oil compounds prompts the use of estimation methods, introducing a challenge in achieving comparable reliability to experimental values. Quantitative comparison of estimation performance shows no distinct trend favoring a singular estimation method, a composite of approaches is suggested to enhance overall model precision. To propel the field forward, a critical need is identified for augmented availability of reliable experimental phase equilibrium data for both pyrolysis bio-oil and its constituent compounds, coupled with their thermophysical properties, to establish a robust foundation for the widespread and efficient application of pyrolysis bio-oil across diverse industries.