What are key challenges while testing a software application?

Test entire application – It is virtually impossible to test and verify entire application with each and every scenario. Even one of the seven principles of software testing says, “Exhaustive Testing is Not Possible”.
Relationship with developers: Tester’s responsibility to check for any defects in the software and how to break an application, it becomes tough to keep amicable relations hip with developers
Regression testing: In every build released from developer, tester has to check entire application for end to end functionality every time along with resolved defect and components or units that are integrated that may get affected due to change request or resolved defect.
Testing always under time constraint: All the stack holders keep an eye on how the built has came out, testers has to quickly start testing the build with sanity test, smoke test and regression tests as send their observations as soon as possible.
Which tests to execute first? – Based on available timeline, and complexity of modules, test lead has to distribute testing like user interface or feature testing using script automatically and regression and integration tests manually. Non functional testing using tools like load runner, API testing using Postman or REST assured. Regression tests using selenium and mobile testing using Appium.
Understanding the requirements: There should be a walkthrough and review of software, domain knowledge, how to test features etc. is mandatory for each member of tester.
Decision to stop the testing: Testing manager should explain testers when should testing be stopped, based on what critical bugs should get resolved, any blockers affecting feature pending by developers.