Nexus is the legal word for "enough presence in a state that the state can make you collect its sales tax." Before 2018 it mostly meant physical presence. Since the Supreme Court's decision in South Dakota v. Wayfair, sales volume alone creates it. For a Shopify store shipping nationwide, that changes the question from "where am I located" to "where are my customers."
Physical nexus: where your business touches the ground
You have physical nexus in any state where the business has a footprint: your home office, a warehouse, an employee or contractor working there, or inventory stored in the state. That last one bites sellers who also use Amazon FBA, because stock sitting in a fulfillment center can create nexus in that state. A store run from a spare bedroom in Texas with a 3PL in Nevada likely has physical nexus in both.
Economic nexus after Wayfair
Economic nexus is presence by revenue. Each state sets its own threshold, and the most common trigger is $100,000 of sales into the state over the current or prior calendar year. Some states also or instead count transactions, historically 200 orders, though a number of states have dropped the transaction test. The exact rules vary state by state and do change, so treat any list as a starting point and confirm against each state's current guidance.
The practical workflow: pull a sales-by-state report from Shopify at least quarterly. Any state where you are approaching six figures of sales deserves a look at its specific threshold, what sales count toward it, and whether your product is even taxable there. Once you cross a threshold, the sequence is register for a permit first, then start collecting. Collecting tax in a state where you never registered is its own problem, since you would be holding tax money with no account to remit it to.
Why Shopify does not remit for you
Here is the trap in the question itself: Shopify is not a marketplace facilitator. Marketplace facilitator laws make Amazon, Etsy, and Walmart collect and remit sales tax on behalf of their third-party sellers in essentially every state with a sales tax. Shopify is a platform you rent, not a marketplace that sells for you, so those laws do not apply. Shopify Tax can calculate the right rate at checkout and warn you as you approach thresholds, but registering, filing the returns, and sending the money remain your job in every state where you have nexus.
For hybrid sellers this splits cleanly: your Amazon sales are generally covered by Amazon's facilitator collection, while your Shopify sales are on you. Note that in many states, marketplace sales still count toward your economic nexus threshold even though the marketplace remitted the tax, which can pull your Shopify sales into a filing obligation sooner than expected.