目前尚不清楚您所说的“最佳方式”是什么意思；如果您想按Split .的每个字符串，并摆脱常见块，即

  Project        Project       - these chunks should be 
  Repositories   Repositories  - removed (they are same in both strings)
  Methods        DataSets
                 Project
                 Repositories
                 Entity 

您可以尝试使用 Linq ，例如

  using System.Linq;

  ...

  string prefix = "Project.Repositories.Methods";
  string source = "Project.Repositories.DataSets.Project.Repositories.Entity";

  string[] prefixes = prefix.Split('.');

  string result = string.Join(".",source
    .Split('.')                                            // split into 
    .Select((value,index) => new { value,index})         // chunks  
    .SkipWhile(item => item.index < prefixes.Length &&     // skip
                       prefixes[item.index] == item.value) // common chunks
    .Select(item => item.value));

  Console.Write(result);

结果：

  DataSets.Project.Repositories.Entity

编辑：否，基于 urbanSoft的答案：

  string prefix = "Project.Repositories.Methods";
  string source = "Project.Repositories.DataSets.Project.Repositories.Entity";

  // We have 2 cases when all starting characters are equal:
  string result = prefix.Length >= source.Length 
    ? ""
    : source.Substring(source.IndexOf('.',prefix.Length) + 1);

  for (int i = 0,dotPosition = -1; i < Math.Min(prefix.Length,source.Length); ++i) {
    if (prefix[i] != source[i]) {
      result = source.Substring(dotPosition + 1);

      break;
    }
    else if (prefix[i] == '.')
      dotPosition = i;
  }

  Console.Write(result);

  

不仅仅是第一部分

如果只有第一部分很重要，为什么不简单地迭代直到第一个字符不匹配呢？

更新了我的答案，以考虑到@Dmitry Bychenko的评论。

string a = "Project.Repositories.Data";
string b = "Project.Repositories.DataSets.Project.Repositories.Entity";
int dotIdx = 0;
for (int i = 0; i < a.Length; i++)
    if (a[i] != b[i])
        break;
    else
        dotIdx = a[i] == '.' ? (i+1) : dotIdx;
Console.WriteLine(b.Substring(dotIdx));