V4.2 to V4.6

I currently have a website running 4.2, can I upgrade straight to 4.6? if I can is there anything I should no?

I am currently backing everything up.

No.  See the docs
https://docs.nopcommerce.com/en/installation-and-upgrading/upgrading-nopcommerce.html
I.e., you will need to run SQL scripts initially.

I thought that might be the case, do I have to go every minor release so I see 4.40.1  4.40.2 etc. or can I just go 4.30 4.40 4.50 ?

Also I do I need to upload each version files and run the website or can I just upload 4.6 files and run the upgrade scripts on SQL database?

First, execute the scripts for versions 4.20 and 4.30, and then proceed to run nopCommerce 4.6.x directly on the migrated database.
No need to check minor versions.
You can check this related thread Upgrade 4.2 to 4.50

//Rashed

Make sure your backups are good.  Better yet, consider creating a new DB & site.  Test it, and then you could adjust your 'infrastructure' to point to new site (depends on your IIS vs hosting, etc.).
-Restore the DB backup to a new DB.   Then run upgrade scripts on it.  
-Copy site files to new folder / set up new site (IIS or similar).
-Adjust new site's /App_Data/dataSettings.json to point to new DB.
  (Note, when site auto-upgrades, dataSettings.json will be replaced with appsettings.json)

please note i am running this on my internal server so I can go over the whole thing before running on my live server.

so 4.2 to 4.3 went perfect, 4.3 to 4.6 , I uploaded the files, replaced my json files , copied all our images etc. loaded the site but getting the below.

HTTP Error 500.30 - ASP.NET Core app failed to start

In Event Viewer - there were a couple more errors as well but all seem to be around the login process and certificate chain.

There was an exception checking if table MigrationVersionInfo in  exists

Exception:
Microsoft.Data.SqlClient.SqlException (0x80131904): A connection was successfully established with the server, but then an error occurred during the login process. (provider: SSL Provider, error: 0 - The certificate chain was issued by an authority that is not trusted.)

Just did a test, and got it to 4.4, but again, the same error going from 4.4 to  4.5

Update - getting these errors now.

Application: w3wp.exe
CoreCLR Version: 6.0.522.21309
.NET Version: 6.0.5
Description: The process was terminated due to an unhandled exception.
Exception Info: System.IO.FileNotFoundException: Could not load file or assembly 'Ubiety.Dns.Core, Version=2.2.1.0, Culture=neutral, PublicKeyToken=, processorArchitecture=MSIL'. The system cannot find the file specified.
File name: 'Ubiety.Dns.Core, Version=2.2.1.0, Culture=neutral, PublicKeyToken=, processorArchitecture=MSIL'


Application '/LM/W3SVC/9/ROOT' with physical root 'F:\WebSites\AAH Live Website\' hit unexpected managed exception, exception code = '0xe0434352'. First 30KB characters of captured stdout and stderr logs:
Unhandled exception. System.IO.FileNotFoundException: Could not load file or assembly 'Ubiety.Dns.Core, Version=2.2.1.0, Culture=neutral, PublicKeyToken=c5687fc88969c44d, processorArchitecture=MSIL'. The system cannot find the file specified.
File name: 'Ubiety.Dns.Core, Version=2.2.1.0, Culture=neutral, PublicKeyToken=, processorArchitecture=MSIL'

Application '/LM/W3SVC/9/ROOT' with physical root 'website' failed to load coreclr. Exception message:
CLR worker thread exited prematurely

tt87 wrote:
Then I suggest you first install a brand new site from scratch.  I.e., use no-source files, do not add any json files, go through first time installation, create new test DB.

It's okay I found the issue, the connection string needed TrustServerCertificate=True; added.