When comparing Substance Painter vs ZBrush, the Slant community recommends Substance Painter for most people. In the question“What are the best 3D texture painting softwares?” Substance Painter is ranked 2nd while ZBrush is ranked 7th. The most important reason people chose Substance Painter is:
Since Substance Painter allows users to paint in full 3D, it can be used not only to paint full textures, but can also paint masks which can then be used in other tools (like Substance Designer) for material filter generators (like the ones used to make edge wear and dirt)
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Pros
Pro Allows you to paint in full 3D
Since Substance Painter allows users to paint in full 3D, it can be used not only to paint full textures, but can also paint masks which can then be used in other tools (like Substance Designer) for material filter generators (like the ones used to make edge wear and dirt)
Pro Painting and procedural editing of textures
Pro Plays well with others
Can transfer work between other packages via AppLink and/or Bridge seamlessly.


Pro Powerful brush system allows for lots of creativity
ZBrush lets the user sculpt an object in fine detail with customizable 3D brushes.
Pro Best for hi-poly modeling
Due to the nature of the program and how it uses high poly mesh sculpting it is best to consider this app when wanting high poly models, as that is what it aims to do best.
Pro Has low poly modelling tools with 4r7 version


Pro Can easily simplify mesh topology
Meshes sculpted with ZBrush can contain billions of polygons, but tools are provided to cleanly reduce the poly count.
Pro Always evolving and innovating
Every iteration of Zbrush has evolved beyond the last and has kept all other 3D package devs on their toes consistently.
Pro Best support
No other 3D package has had continued support from their parent company or community like ZBrush has had since inception.
Cons
Con Expensive and impossible to run without an expensive graphics card
The free trial is the only thing free. You'll have to pay a lot of money for the full version, and even if you do get it, you will have to pay for an expensive graphics card to use it, which means a lot more money flying out of your wallet and/or bank account.
Con Cannot export in a procedural format
You can not export substance (sbsar) files in Painter.
Con UI is far from user friendly
Though, it's fully customizable. Like for any software, there is a learning curve.

Con Expensive
A single-user license for ZBrush costs $795.
But, Pixologic has not charged a penny for upgrades to licensed users since inception. Anyone who has purchased Zbrush has not been left behind.
Con An odd perspective view
Does not lend itself to cinematic or artistic renderings due to a strange perspective system found nowhere else in 3D which warps according to the relationships between models and rendering viewpoint - there is no real 'camera'.
It is sufficient for rendering your work on a sculptural piece or industrial design, but KeyShot Pro or any other PBR rendering program that uses a camera are recommended for scene rendering, at least in 4R7.
Con Open, Save, Export, Import not conventional standard UI
Authors refuse to use standard layout and the New, Open, Save, Export, Import are in unexpected positions. There will be no UI improvements.
Con Hi-poly only
Not, the case as there is now the Zmodeller Brush system which has a full suite of polygon Modelling options.
