Can I design PAGX layouts shared in ArcGIS Online in VSP Designer with ArcGIS Pro Layout Mode active?

Yes. Since the release of the gen2 SaaS instance of the Printing Engine, it is now possible to design and edit ArcGIS Pro layouts stored in ArcGIS Online (AGOL) using VSP Designer with ArcGIS Pro Layout Mode active.
Both deployment options of Printing Designer support this capability:

• SaaS instance of Printing Designer
• On‑premises installation of Printing Designer

With either version, you can open and edit gen2 layouts that are stored in your ArcGIS Online organization.
 

Using the SaaS Instance of Printing Designer

This instance of the Printing Designer is already configured to be accessed with your ArcGIS Online login.
 

Using an On‑Premises Printing Designer with the SaaS Printing Engine

When using an on‑premises Designer, you can configure it to use the new SaaS Printing Engine by specifying the corresponding service URL in the Designer configuration.
This allows the on‑premises Designer to take advantage of the SaaS rendering engine while still operating locally.

Important Requirement: ArcGIS Online Must Be Configured as the Authentication Portal

While the SaaS engine enables rendering and editing support, the SaaS engine alone is not sufficient for editing layouts stored in ArcGIS Online. To access and modify AGOL‑hosted layouts using an on‑premises Designer, you must configure ArcGIS Online as the authentication portal via the Printing Designer Post‑Installer.

This ensures that user authentication and permissions align with AGOL requirements and enables the Designer to open, edit, and save layouts stored in the cloud.