To create and configure a VPC, I first create the VPC with a suitable CIDR range, then create public and private subnets across multiple Availability Zones. Next, I attach an Internet Gateway, configure route tables, and create a NAT Gateway for internet access from private subnets. I then configure Security Groups and NACLs, launch resources in the appropriate subnets, and enable monitoring using VPC Flow Logs and CloudWatch. This design ensures security, scalability, and high availability.