Company: TEM
Filing Date: 2025-08-27
Form Type: 424B7
Source: 0001193125-25-189854
Chunk: 1

Company: Tempus AI, Inc.
Filing Date: 2025-08-27
Form: 424B7
Chunk 1
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 not selling any shares under this prospectus
supplement and will not receive any proceeds from any sale of shares by the selling stockholders. We, and not the selling stockholders, will pay the costs, expenses and fees in connection with the registration of the shares of Class A common
stock covered by this prospectus supplement, but the selling stockholders will pay all discounts, commissions or brokers’ fees or fees of similar securities industry professionals and transfer taxes, if any, attributable to sales of such
shares of Class A common stock.

We are registering the resale of the shares of Class A common stock held by the selling stockholders to permit
the selling stockholders to resell or otherwise dispose of such shares in the manner contemplated under “Plan of Distribution.” See the section titled “Plan of Distribution” for more information.

Our shares of Class A common stock are listed on the Nasdaq Global Select Market (“Nasdaq”) under the symbol “TEM.” On
August 26, 2025, the closing sale price of our Class A common stock was $76.30 per share.

Investing in our Class A common stock involves risks that are described in the section titled “ Risk Factors” beginning on page S-7of this prospectus supplement.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of the securities to be sold under this prospectus supplement or determined if this prospectus supplement is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus supplement is August 27, 2025.

TABLE OF CONTENTS Prospectus Supplement

|                                                   |     | Page |      |
| ABOUT THIS PROSPECTUS SUPPLEMENT                  |     |      | S-1  |
| SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS |     |      | S-3  |
| THE COMPANY                                       |     |      | S-5  |
| RISK FACTORS                                      |     |      | S-7  |
| USE OF PROCEEDS                                   |     |      | S-8  |
| SELLING STOCKHOLDERS                              |     |      | S-9  |
| PLAN OF DISTRIBUTION                              |     |      | S-11 |
| LEGAL MATTERS                                     |     |      | S-13 |
| EXPERTS                                           |     |      | S-13 |
| WHERE YOU CAN FIND MORE INFORMATION               |     |      | S-14 |
| INCORPORATION OF CERTAIN