Among the challenges of collecting sales tax is there are thousands of taxing jurisdictions. And often the boundaries don't correspond to any zipcode nor even a particular municipality. In addition, sales tax jurisdictions can and often do overlap - ie. city and county.
Even a state that doesn't levy a sales tax itself may allow local authorities to do so, such as some local Alaskan towns do.
To make matters worse, there are numerous categories and exceptions in what's taxable depending on what it is, the amount purchased, the location / manner in which it's sold (ie. food item purchased in a convenience store verses supermarket; consumed on premises or take-out) and when (tax holidays, etc).
And then there's the matter of filing dozens of state sales tax returns - some will expect filings every month, some quarterly, etc. And the time-frames will often differ, so one could find themselves filing sales tax forms practically every month or even more often depending on sales volume. And that's not even getting into dealing with compliance checks that states may perform at any time.
Bottom line is sales tax is far more challenging to collect than many realize. It's not 50 states, but rather thousands of taxing jurisdictions with numerous different rates, rules, exemptions, etc.
There is talk of simplifying the collection process for on-line retailers, which would lessen the burden, especially to small businesses.