Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants. Synopsis: SARS-CoV-2 evolution leads to the rapid and continuous emergence of sub-variants. This study identifies key amino acids which mediate sub-variant infection potential by balancing host receptor binding affinity and immune escape. The cryo-EM structures of the receptor binding domains (RBDs) of Omicron sub-variants BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 in complex with human ACE2 were determined. R346T substitution enhances ACE2 binding via an interplay with R493, but not Q493 substitution, due to long-range conformation alterations. The mutations R493Q and F486V maintain an optimal receptor binding affinity of the RBD, while R493Q reduces immune evasion capability. Cryo-EM structures of Omicron sub-variant receptor binding domains with human ACE2 receptor reveal the key residues that balance receptor binding and immune evasion potential. [ABSTRACT FROM AUTHOR]