Would you offer immunotherapy for recurrent metastatic Ewing sarcoma if the tumor is MSI high or has high TMB?  

Yes, though this is an unlikely event given the transcription factor driven disease. NCCN lists pembro for TMB-H or MSI-H tumors, though I do not think any of the trials included Ewing Sarcoma. Probably better to use salvage regimens such as cyclo/topo or iri/temo first. Then work way to multikinase...

Limited data available (e.g.from SARC 028 - Tawbi et al., PMID 28988646) does not suggest any reasonable activity of CPI in Ewing sarcoma subset. Treating the patient on a "basket trial" of TMB-H or MSI-H would be reasonable, but not as standard of care.